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Article(id=1322926378806551068, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.08.022, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793339827490, onlineDateStr=2026-10-30, pubDate=1754755200000, pubDateStr=2025-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339827490, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339827490, creator=13701087609, updateTime=1793339827490, updator=13701087609, issue=Issue{id=1322926217711726961, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='8', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1754755200000', pubDateStr='2025-08-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339789083, creator='13701087609', updateTime=1793340517761, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929274071679978, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929274071679979, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=101, endPage=110, ext={EN=ArticleExt(id=1322926379095958045, articleId=1322926378806551068, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Comparison of Glycosides of Leigongteng（Tripterygium wilfordii）on Toxic Damage in Male Rats of Different Ages, columnId=1256183361521967297, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Target on National Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To compare the toxic effects of glycosides of Leigongteng（Tripterygium wilfordii）（GTW）on liver，blood and reproductive system in male rats of different ages.

Methods

Fifty-six male Sprague-Dawley（SD）rats aged 3，5 and 10 weeks and 8 months（equivalent to pre-school age，school age，adolescence and adulthood）were selected.The each age group was divided into control group and GTW group by random number table method.The GTW group was given 12.5 mg/（kg·d）［equivalent to2 mg/（kg·d）for children］GTW suspension，and the control group was given the same amount of normal saline.Seven rats in each age group were taken from the control group and GTW group at 2，4，8 and 12 weeks，respectively，and the organ indexes of liver，testis and epididymis were calculated.Blood routine indexes were detected by automatic blood cell analyzer.Liver function indexes were detected by automatic dry biochemical analyzer.The serum levels of testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH）and estradiol（E2）were detected by ELISA.The histopathological changes of liver，testis and epididymis were observed by HE staining.Sperm density and viability were calculated under light microscope.ImajeJ software counted the proportion of spermatogonia，spermatocytes and spermatids in the seminiferous tubules of the testis.

Results

From the perspective of the liver system，there was no significant increase in liver index in rats of all age groups during GTW intervention.Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）increased at the 4th and 8th week（P<0.05），and recovered at the 12th week.The pathological morphology of the liver showed that the degree of liver damage increases with the time of gastric lavage，and there was no significant difference between different age groups.From the perspective of the blood system，a decrease in PLT（P<0.05）appeared earliest and recovered by the 12th week.The rats aged 5 and 10 weeks showed a decrease in white blood cell（WBC）at 4th week（P<0.05）and recovered at 12th week.The decrease in hemoglobin（HB）（P<0.05）appeared the latest and all except for 3-week-old rats recovered at 12th week.From the perspective of the reproductive system，5-week-old and 8-month-old rats showed a decrease in T at the 4th week（P<0.05），followed by a decrease in T in all rats（P<0.05）.Except for 3-week-old rats，all other rats showed a decrease in sperm density in the second week（P<0.05），while 8-month-old rats showed the earliest decrease in sperm density and viability in the 4th week（P<0.05）.In the second week，8-month-old rats showed a decrease in the proportion of sperm cells at the earliest stage（P<0.05）.Pathology of the testes and epididymis both showed severe damage in 8-month-old rats.

Conclusion

①There was no significant difference in liver damage caused by GTW in rats of different age groups，but it worsened with medication time.②The toxicity of GTW to the blood system is manifested by inconsistent decreases in blood routine indicators，and young rats are more intolerant to blood damage caused by GTW than adult rats.③Compared to young rats，adult rats are more sensitive to the reproductive toxicity of GTW.

, authors=Zhaoheng SUN1, Ying DING1, Shanshan HAN1, Shanshan XU2, Yanlin DAI2, authorsList=Zhaoheng SUN, Ying DING, Shanshan HAN, Shanshan XU, Yanlin DAI, authorCompany=null, correspAuthors=Ying DING, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322926383676138055, articleId=1322926378806551068, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=雷公藤多苷对不同年龄段雄鼠毒性损伤的比较, columnId=1256183362172142382, journalTitle=中华中医药学刊, columnName=国家项目点击, runingTitle=null, highlight=null, articleAbstract=
目的

比较雷公藤多苷（glycosides of tripterygium wilfordii，GTW）对不同年龄段雄鼠肝脏、血液、生殖系统的毒性损伤。

方法

选取3周龄、5周龄、10周龄、8月龄（相当于学龄前期、学龄期、青春期、成人期）SD雄鼠各56只，每个年龄段采用随机数字表法分为空白组和GTW 组，GTW 组给予12.5 mg/（kg·d）［相当于儿童2 mg/（kg·d）］GTW 悬浊液灌胃，空白组给予等量生理盐水灌胃，分别于2、4、8、12周每个年龄段各取7只空白组和GTW 组，计算肝脏、睾丸、附睾脏器指数；全自动血液细胞分析仪检测血常规指标；全自动干式生化分析仪检测肝功能指标；ELISA法检测睾酮、促卵泡生成素、促黄体生成素及雌二醇水平；HE染色法观察大鼠肝脏、睾丸、附睾组织病理改变；光学显微镜下计算精子密度和活率；ImajeJ软件统计睾丸生精小管内精原细胞、精母细胞、精子细胞的比例。

结果

从肝脏系统来看，各年龄段大鼠在GTW干预期间未出现肝脏指数明显升高，第4周、第8周出现丙氨酸氨基转移酶、天冬氨酸氨基转移酶升高（P<0.05），第12周恢复；肝脏病理形态显示肝脏损伤程度随灌胃时间而加重，而各年龄段之间的损伤程度未见明显差异。从血液系统来看，血小板减少（P<0.05）最早出现，第12周恢复；5周龄、10周龄大鼠第4周出现白细胞减少（P<0.05），第12周恢复；血红蛋白减少（P<0.05）最晚出现，除3周龄大鼠外均在第12周恢复。从生殖系统来看，5周龄、8月龄大鼠于第4周出现睾酮下降（P<0.05），而后所有大鼠睾酮均下降（P<0.05）；除3周龄大鼠外其余均在第2周出现精子密度下降（P<0.05），第4周8月龄大鼠最早出现精子密度、活率均下降（P<0.05）；第2周8月龄大鼠最早出现精子细胞比例下降（P<0.05）；睾丸、附睾病理均显示8月龄大鼠损伤较重。

结论

①GTW 对不同年龄段大鼠的肝脏损伤无明显差异，但随用药时间而加重；②GTW 对血液系统的毒性表现为血常规指标下降的不一致性，且幼鼠较成鼠更不耐受GTW 造成的血液损伤。③相对幼鼠，成鼠对GTW 的生殖毒性更为敏感。

, authors=孙昭恒1, 丁樱1, 韩姗姗1, 徐闪闪2, 代彦林2, authorsList=孙昭恒, 丁樱, 韩姗姗, 徐闪闪, 代彦林, authorCompany=null, correspAuthors=丁樱, authorNote=

孙昭恒（1995-），女，河南郑州人，博士在读，研究方向：中医药防治小儿肾脏病。

, correspAuthorsNote=
丁樱（1951-），女，江苏南京人，主任医师、教授，国医大师，国家首批名中医，学士，研究方向：小儿肾脏病。E-mail：。
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孙昭恒（1995-），女，河南郑州人，博士在读，研究方向：中医药防治小儿肾脏病。

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孙昭恒（1995-），女，河南郑州人，博士在读，研究方向：中医药防治小儿肾脏病。

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鼠龄组别n干预2周干预4周
肝脏指数睾丸指数附睾指数肝脏指数睾丸指数附睾指数
3周龄空白组74.300±0.2430.977±0.0310.147±0.1273.658±0.3320.982±0.0660.242±0.026
GTW组74.076±0.1460.947±0.0400.148±0.1263.306±0.1510.891±0.0700.197±0.028
F值1.7500.2510.1401.4750.0012.619
P值0.0580.1450.9320.0940.0280.009
5周龄空白组73.648±0.2610.965±0.0580.221±0.0352.917±0.1000.803±0.1080.292±0.026
GTW组73.482±0.1390.947±0.0550.214±0.0212.823±0.2180.765±0.1300.253±0.044
F值5.0090.2435.0791.9420.0640.875
P值0.1720.5770.6640.3230.9490.067
10周龄空白组72.910±0.2970.727±0.0240.298±0.0213.052±0.2560.694±0.0900.272±0.030
GTW组72.809±0.1420.783±0.1200.284±0.0422.947±0.1090.781±0.0790.253±0.045
F值1.89211.8563.9365.4050.1691.340
P值0.4290.2750.4270.3470.0780.114
8月龄空白组72.183±0.2150.542±0.0990.214±0.0142.169±0.1110.505±0.0230.198±0.015
GTW组72.192±0.1660.538±0.1200.215±0.0242.322±0.2420.577±0.1170.183±0.039
F值0.9070.3941.8859.1095.4925.586
P值0.9300.9480.8900.1640.1580.374
), ArticleFig(id=1322926388835132030, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表1, caption=

雷公藤多苷干预2周、4周后不同年龄段大鼠脏器指数比较（±s）

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鼠龄组别n干预2周干预4周
肝脏指数睾丸指数附睾指数肝脏指数睾丸指数附睾指数
3周龄空白组74.300±0.2430.977±0.0310.147±0.1273.658±0.3320.982±0.0660.242±0.026
GTW组74.076±0.1460.947±0.0400.148±0.1263.306±0.1510.891±0.0700.197±0.028
F值1.7500.2510.1401.4750.0012.619
P值0.0580.1450.9320.0940.0280.009
5周龄空白组73.648±0.2610.965±0.0580.221±0.0352.917±0.1000.803±0.1080.292±0.026
GTW组73.482±0.1390.947±0.0550.214±0.0212.823±0.2180.765±0.1300.253±0.044
F值5.0090.2435.0791.9420.0640.875
P值0.1720.5770.6640.3230.9490.067
10周龄空白组72.910±0.2970.727±0.0240.298±0.0213.052±0.2560.694±0.0900.272±0.030
GTW组72.809±0.1420.783±0.1200.284±0.0422.947±0.1090.781±0.0790.253±0.045
F值1.89211.8563.9365.4050.1691.340
P值0.4290.2750.4270.3470.0780.114
8月龄空白组72.183±0.2150.542±0.0990.214±0.0142.169±0.1110.505±0.0230.198±0.015
GTW组72.192±0.1660.538±0.1200.215±0.0242.322±0.2420.577±0.1170.183±0.039
F值0.9070.3941.8859.1095.4925.586
P值0.9300.9480.8900.1640.1580.374
), ArticleFig(id=1322926388931601023, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n干预8周干预12周
肝脏指数睾丸指数附睾指数肝脏指数睾丸指数附睾指数
3周龄空白组72.916±0.3290.731±0.1610.275±0.0372.421±0.0870.772±0.0890.258±0.040
GTW组72.901±0.1980.714±0.0420.259±0.0292.547±0.1620.721±0.0570.244±0.018
F值2.7891.3420.0391.0172.7834.119
P值0.9220.1800.3910.0880.2080.377
5周龄空白组72.364±0.1740.835±0.0910.261±0.0352.422±0.1800.775±0.0570.245±0.014
GTW组72.459±0.1500.672±0.1410.242±0.0452.418±0.0900.661±0.0390.206±0.043
F值0.2770.1860.9752.9881.0482.492
P值0.2970.0240.3990.958<0.010.013
10周龄空白组72.415±0.1770.789±0.0990.275±0.0201.865±0.7380.714±0.0940.284±0.024
GTW组72.323±0.1470.764±0.0420.247±0.0222.096±0.1430.694±0.0890.239±0.022
F值0.1821.1450.5640.1920.1700.209
P值0.3090.5530.0290.8480.7020.003
8月龄空白组72.158±0.1290.672±0.1160.2502.282±0.2330.644±0.0500.295±0.087
GTW组72.214±0.5240.539±0.1620.1732.188±0.3910.428±0.1310.168±0.027
F值6.4890.5833.1302.4503.1303.130
P值0.7930.1030.0020.5950.0020.002
), ArticleFig(id=1322926389007098496, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表2, caption=

雷公藤多苷干预8周、12周后不同年龄段大鼠脏器指数比较（）

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鼠龄组别n干预8周干预12周
肝脏指数睾丸指数附睾指数肝脏指数睾丸指数附睾指数
3周龄空白组72.916±0.3290.731±0.1610.275±0.0372.421±0.0870.772±0.0890.258±0.040
GTW组72.901±0.1980.714±0.0420.259±0.0292.547±0.1620.721±0.0570.244±0.018
F值2.7891.3420.0391.0172.7834.119
P值0.9220.1800.3910.0880.2080.377
5周龄空白组72.364±0.1740.835±0.0910.261±0.0352.422±0.1800.775±0.0570.245±0.014
GTW组72.459±0.1500.672±0.1410.242±0.0452.418±0.0900.661±0.0390.206±0.043
F值0.2770.1860.9752.9881.0482.492
P值0.2970.0240.3990.958<0.010.013
10周龄空白组72.415±0.1770.789±0.0990.275±0.0201.865±0.7380.714±0.0940.284±0.024
GTW组72.323±0.1470.764±0.0420.247±0.0222.096±0.1430.694±0.0890.239±0.022
F值0.1821.1450.5640.1920.1700.209
P值0.3090.5530.0290.8480.7020.003
8月龄空白组72.158±0.1290.672±0.1160.2502.282±0.2330.644±0.0500.295±0.087
GTW组72.214±0.5240.539±0.1620.1732.188±0.3910.428±0.1310.168±0.027
F值6.4890.5833.1302.4503.1303.130
P值0.7930.1030.0020.5950.0020.002
), ArticleFig(id=1322926389103567489, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组78.657±3.352147.857±6.2831138±103.02172.571±16.950178.714±57.812
GTW组75.571±1.999152.857±7.5371087±247.27561.429±27.934178.000±63.013
F值2.1851.0971.8530.4720.447
P值0.0580.2730.0640.3850.655
5周龄空白组78.840±3.682160.286±10.5941304±192.52747.429±5.094114.571±21.039
GTW组76.943±1.630164.143±6.694917±125.73466.286±54.218140.714±53.447
F值7.3910.7961.28312.6404.945
P值0.2360.431<0.0010.3940.264
10周龄空白组76.843±2.521174.714±9.2321213±123.78757.714±3.946179.143±26.636
GTW组75.400±2.226174.000±9.950840±137.00860.000±6.429153.000±18.403
F值0.3960.4870.0080.4500.395
P值0.2790.892<0.0010.6530.054
8月龄空白组76.943±1.976163.857±10.2861649±296.79848.000±15.416149.143±24.259
GTW组76.929±1.147150.857±23.270976±309.04145.857±18.632156.714±59.626
F值2.9701.2152.7470.7045.310
P值0.9870.2240.0060.4820.764
), ArticleFig(id=1322926389195842178, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表3, caption=

雷公藤多苷干预2周后不同年龄段大鼠血常规、肝肾功指数比较（）

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鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组78.657±3.352147.857±6.2831138±103.02172.571±16.950178.714±57.812
GTW组75.571±1.999152.857±7.5371087±247.27561.429±27.934178.000±63.013
F值2.1851.0971.8530.4720.447
P值0.0580.2730.0640.3850.655
5周龄空白组78.840±3.682160.286±10.5941304±192.52747.429±5.094114.571±21.039
GTW组76.943±1.630164.143±6.694917±125.73466.286±54.218140.714±53.447
F值7.3910.7961.28312.6404.945
P值0.2360.431<0.0010.3940.264
10周龄空白组76.843±2.521174.714±9.2321213±123.78757.714±3.946179.143±26.636
GTW组75.400±2.226174.000±9.950840±137.00860.000±6.429153.000±18.403
F值0.3960.4870.0080.4500.395
P值0.2790.892<0.0010.6530.054
8月龄空白组76.943±1.976163.857±10.2861649±296.79848.000±15.416149.143±24.259
GTW组76.929±1.147150.857±23.270976±309.04145.857±18.632156.714±59.626
F值2.9701.2152.7470.7045.310
P值0.9870.2240.0060.4820.764
), ArticleFig(id=1322926389296505475, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.329±2.837158.286±8.1591206±142.74354.429±13.624169.429±57.460
GTW组76.371±3.668161.857±3.6251055±80.035110.000±12.754219.143±36.030
F值0.2595.2683.6520.4672.246
P值0.1170.3110.031<0.0010.025
5周龄空白组79.314±1.497158.857±8.3751315±128.02181.571±67.431249.429±196.423
GTW组75.357±1.361162.571±7.5251034±171.557103.000±13.976257.143±54.819
F值0.0010.0100.2512.2361.342
P值<0.0010.4000.0050.0250.180
10周龄空白组79.600±2.310160.286±7.0641203±102.86758.286±13.889176.571±46.335
GTW组74.800±2.587168.571±8.284867±190.41584.857±23.205247.286±111.852
F值2.7470.0823.1301.7913.028
P值0.0060.0670.0020.0230.148
8月龄空白组75.171±0.909163.143±12.4151420±235.88944.286±5.589116.571±24.110
GTW组75.300±1.672167.571±11.163859±120.369131.429±57.081311.429±110.670
F值1.5380.0002.1756.8493.134
P值0.8610.496<0.0010.0070.002
), ArticleFig(id=1322926389397168772, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表4, caption=

雷公藤多苷干预4周后不同年龄段大鼠血常规、肝肾功指数比较（）

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鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.329±2.837158.286±8.1591206±142.74354.429±13.624169.429±57.460
GTW组76.371±3.668161.857±3.6251055±80.035110.000±12.754219.143±36.030
F值0.2595.2683.6520.4672.246
P值0.1170.3110.031<0.0010.025
5周龄空白组79.314±1.497158.857±8.3751315±128.02181.571±67.431249.429±196.423
GTW组75.357±1.361162.571±7.5251034±171.557103.000±13.976257.143±54.819
F值0.0010.0100.2512.2361.342
P值<0.0010.4000.0050.0250.180
10周龄空白组79.600±2.310160.286±7.0641203±102.86758.286±13.889176.571±46.335
GTW组74.800±2.587168.571±8.284867±190.41584.857±23.205247.286±111.852
F值2.7470.0823.1301.7913.028
P值0.0060.0670.0020.0230.148
8月龄空白组75.171±0.909163.143±12.4151420±235.88944.286±5.589116.571±24.110
GTW组75.300±1.672167.571±11.163859±120.369131.429±57.081311.429±110.670
F值1.5380.0002.1756.8493.134
P值0.8610.496<0.0010.0070.002
), ArticleFig(id=1322926389485249157, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.429±2.564165.286±9.4821306±266.92254.429±10.814189.571±72.092
GTW组79.300±3.331146.714±9.7681080±97.18578.571±16.430200.571±61.951
F值0.4490.0125.2280.4350.084
P值0.6530.0040.0700.0070.765
5周龄空白组79.329±1.387163.286±10.2421494±133.36643.857±9.737150.143±31.504
GTW组79.100±3.270151.286±5.9921248±436.32954.143±7.381135.000±38.588
F值12.5061.2372.2360.0600.324
P值0.8680.0200.0250.0460.437
10周龄空白组78.929±0.879160.000±12.3151143±87.94545.571±8.979213.000±35.242
GTW组76.000±1.661161.571±7.5911218±105.83294.429±28.664209.857±41.547
F值0.7660.9040.1584.7590.043
P值0.0010.7790.1760.0010.881
8月龄空白组74.600±1.884157.571±5.2871375±226.73349.857±15.082116.286±35.008
GTW组75.443±0.447154.714±8.4001131±115.41678.143±19.377209.286±42.863
F值2.7881.4852.6192.2392.878
P值0.2720.4740.0090.0250.004
), ArticleFig(id=1322926389564940934, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表5, caption=

雷公藤多苷干预8周后不同年龄段大鼠血常规、肝肾功指数比较（）

, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.429±2.564165.286±9.4821306±266.92254.429±10.814189.571±72.092
GTW组79.300±3.331146.714±9.7681080±97.18578.571±16.430200.571±61.951
F值0.4490.0125.2280.4350.084
P值0.6530.0040.0700.0070.765
5周龄空白组79.329±1.387163.286±10.2421494±133.36643.857±9.737150.143±31.504
GTW组79.100±3.270151.286±5.9921248±436.32954.143±7.381135.000±38.588
F值12.5061.2372.2360.0600.324
P值0.8680.0200.0250.0460.437
10周龄空白组78.929±0.879160.000±12.3151143±87.94545.571±8.979213.000±35.242
GTW组76.000±1.661161.571±7.5911218±105.83294.429±28.664209.857±41.547
F值0.7660.9040.1584.7590.043
P值0.0010.7790.1760.0010.881
8月龄空白组74.600±1.884157.571±5.2871375±226.73349.857±15.082116.286±35.008
GTW组75.443±0.447154.714±8.4001131±115.41678.143±19.377209.286±42.863
F值2.7881.4852.6192.2392.878
P值0.2720.4740.0090.0250.004
), ArticleFig(id=1322926389632049799, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.257±0.844162.000±7.6161934±605.09357.571±27.397159.714±52.955
GTW组78.429±1.001154.571±4.2371356±465.97449.143±3.437121.000±16.921
F值0.0120.7051.53511.3599.564
P值0.1200.0440.1250.4350.107
5周龄空白组79.043±0.683156.286±7.3871427±99.04748.143±10.699174.429±46.626
GTW组79.543±1.557157.429±6.8521574±171.86843.571±3.867156.429±29.540
F值3.2950.0043.9143.3753.057
P值0.4510.7690.0750.3090.405
10周龄空白组79.143±0.663142.286±7.2511159±141.36279.286±42.727154.714±94.704
GTW组77.671±2.464147.429±9.2891307±226.49956.857±12.536133.143±43.364
F值4.0180.1780.6971.2210.064
P值0.1530.2710.1680.2220.949
8月龄空白组74.929±0.512150.857±9.9071367±201.49170.000±27.791133.286±20.637
GTW组75.143±0.943152.857±9.0081257±181.22366.143±17.837179.286±53.178
F值1.2290.0361.3420.3842.056
P值0.6070.7000.1800.7010.040
), ArticleFig(id=1322926389715935880, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表6, caption=

雷公藤多苷干预12周后不同年龄段大鼠血常规、肝肾功指数比较（）

, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n血常规肝功能
WBC/（109/L）HB/（g/L）PLT/（109/L）ALT/（U/L）AST/（U/L）
3周龄空白组79.257±0.844162.000±7.6161934±605.09357.571±27.397159.714±52.955
GTW组78.429±1.001154.571±4.2371356±465.97449.143±3.437121.000±16.921
F值0.0120.7051.53511.3599.564
P值0.1200.0440.1250.4350.107
5周龄空白组79.043±0.683156.286±7.3871427±99.04748.143±10.699174.429±46.626
GTW组79.543±1.557157.429±6.8521574±171.86843.571±3.867156.429±29.540
F值3.2950.0043.9143.3753.057
P值0.4510.7690.0750.3090.405
10周龄空白组79.143±0.663142.286±7.2511159±141.36279.286±42.727154.714±94.704
GTW组77.671±2.464147.429±9.2891307±226.49956.857±12.536133.143±43.364
F值4.0180.1780.6971.2210.064
P值0.1530.2710.1680.2220.949
8月龄空白组74.929±0.512150.857±9.9071367±201.49170.000±27.791133.286±20.637
GTW组75.143±0.943152.857±9.0081257±181.22366.143±17.837179.286±53.178
F值1.2290.0361.3420.3842.056
P值0.6070.7000.1800.7010.040
), ArticleFig(id=1322926389791433353, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7140.563±16.1880.377±0.33063.050±8.17910.583±4.627
GTW组7145.227±46.1210.170±0.08468.992±9.55311.719±1.755
F值0.1923.7310.0452.263
P值0.8480.1330.2350.555
5周龄空白组7170.067±17.9270.710±0.21441.260±9.40714.044±3.838
GTW组7157.157±20.3240.434±0.27154.026±16.59612.544±2.184
F值0.0645.2752.1990.192
P值0.9490.0560.1020.848
10周龄空白组7133.515±39.6741.341±0.89639.664±10.38114.967±4.555
GTW组7145.485±44.1411.142±0.13736.369±7.02715.657±2.486
F值0.0130.7040.9581.506
P值0.6030.4820.3380.731
8月龄空白组7157.961±27.3841.814±0.32669.275±16.57712.822±3.527
GTW组7145.125±25.3851.599±0.17282.865±14.15512.320±2.032
F值0.0180.1740.8263.154
P值0.3810.1470.1250.750
), ArticleFig(id=1322926389871125130, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表7, caption=

雷公藤多苷干预2周后不同年龄段大鼠血清T、FSH、LH、E2含量比较（）

, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7140.563±16.1880.377±0.33063.050±8.17910.583±4.627
GTW组7145.227±46.1210.170±0.08468.992±9.55311.719±1.755
F值0.1923.7310.0452.263
P值0.8480.1330.2350.555
5周龄空白组7170.067±17.9270.710±0.21441.260±9.40714.044±3.838
GTW组7157.157±20.3240.434±0.27154.026±16.59612.544±2.184
F值0.0645.2752.1990.192
P值0.9490.0560.1020.848
10周龄空白组7133.515±39.6741.341±0.89639.664±10.38114.967±4.555
GTW组7145.485±44.1411.142±0.13736.369±7.02715.657±2.486
F值0.0130.7040.9581.506
P值0.6030.4820.3380.731
8月龄空白组7157.961±27.3841.814±0.32669.275±16.57712.822±3.527
GTW组7145.125±25.3851.599±0.17282.865±14.15512.320±2.032
F值0.0180.1740.8263.154
P值0.3810.1470.1250.750
), ArticleFig(id=1322926391540458123, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7160.776±23.7381.840±1.48952.972±12.98811.937±4.664
GTW组7162.431±23.3300.792±0.25851.877±6.68110.928±1.717
F值0.1921.2152.37510.785
P值0.8480.2240.8560.499
5周龄空白组7211.559±31.3401.302±0.49663.406±12.26315.937±7.652
GTW组7182.035±23.0510.813±1.25869.042±8.0779.498±4.873
F值1.0305.4730.9231.597
P值0.0680.0400.3300.110
10周龄空白组7149.695±36.2911.326±0.41753.171±16.34114.993±4.336
GTW组7156.674±17.6271.058±0.48448.522±4.50710.855±3.652
F值3.6341.0865.2961.853
P值0.6550.2270.4820.064
8月龄空白组7168.174±41.1121.521±0.51572.361±11.33311.468±2.788
GTW组7159.555±17.8501.029±0.24767.215±16.5179.160±1.354
F值7.4211.2130.2200.539
P值0.6200.0420.5100.072
), ArticleFig(id=1322926391670481548, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表8, caption=

雷公藤多苷干预4周后不同年龄段大鼠血清T、FSH、LH、E2含量比较（）

, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7160.776±23.7381.840±1.48952.972±12.98811.937±4.664
GTW组7162.431±23.3300.792±0.25851.877±6.68110.928±1.717
F值0.1921.2152.37510.785
P值0.8480.2240.8560.499
5周龄空白组7211.559±31.3401.302±0.49663.406±12.26315.937±7.652
GTW组7182.035±23.0510.813±1.25869.042±8.0779.498±4.873
F值1.0305.4730.9231.597
P值0.0680.0400.3300.110
10周龄空白组7149.695±36.2911.326±0.41753.171±16.34114.993±4.336
GTW组7156.674±17.6271.058±0.48448.522±4.50710.855±3.652
F值3.6341.0865.2961.853
P值0.6550.2270.4820.064
8月龄空白组7168.174±41.1121.521±0.51572.361±11.33311.468±2.788
GTW组7159.555±17.8501.029±0.24767.215±16.5179.160±1.354
F值7.4211.2130.2200.539
P值0.6200.0420.5100.072
), ArticleFig(id=1322926391750173325, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7200.794±34.3891.860±1.46348.570±19.43413.007±6.464
GTW组7174.526±26.8710.579±0.50063.520±7.1048.415±1.766
F值0.7122.2365.0863.364
P值0.1370.0250.0800.095
5周龄空白组7167.465±49.5102.622±0.92558.253±10.57211.938±2.452
GTW组7174.812±32.3570.385±0.22566.864±7.17310.092±3.881
F值3.0768.6480.6881.469
P值0.748<0.0010.1000.142
10周龄空白组7174.750±20.1311.128±0.42857.476±10.22813.789±1.740
GTW组7172.027±27.9230.442±0.16763.235±2.67112.175±2.062
F值0.0644.6983.6590.001
P值0.9490.0020.1750.139
8月龄空白组7178.642±50.2951.544±0.57161.679±20.90212.745±1.151
GTW组7164.206±30.5730.507±0.18367.778±10.45013.154±3.253
F值2.4929.5652.9839.593
P值0.5290.0010.5240.759
), ArticleFig(id=1322926391834059406, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表9, caption=

雷公藤多苷干预8周后不同年龄段大鼠血清T、FSH、LH、E2含量比较（）

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鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7200.794±34.3891.860±1.46348.570±19.43413.007±6.464
GTW组7174.526±26.8710.579±0.50063.520±7.1048.415±1.766
F值0.7122.2365.0863.364
P值0.1370.0250.0800.095
5周龄空白组7167.465±49.5102.622±0.92558.253±10.57211.938±2.452
GTW组7174.812±32.3570.385±0.22566.864±7.17310.092±3.881
F值3.0768.6480.6881.469
P值0.748<0.0010.1000.142
10周龄空白组7174.750±20.1311.128±0.42857.476±10.22813.789±1.740
GTW组7172.027±27.9230.442±0.16763.235±2.67112.175±2.062
F值0.0644.6983.6590.001
P值0.9490.0020.1750.139
8月龄空白组7178.642±50.2951.544±0.57161.679±20.90212.745±1.151
GTW组7164.206±30.5730.507±0.18367.778±10.45013.154±3.253
F值2.4929.5652.9839.593
P值0.5290.0010.5240.759
), ArticleFig(id=1322926391989248655, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7161.830±22.5842.433±0.64962.224±9.81614.487±3.296
GTW组7153.105±19.4620.557±0.21264.607±3.65912.095±1.593
F值2.86211.5136.7836.633
P值0.364<0.0010.5580.109
5周龄空白组7160.310±25.1131.395±0.59460.649±8.25914.546±2.426
GTW组7140.314±15.7260.610±0.13063.201±4.96712.824±3.354
F值2.1355.4022.6200.846
P值0.0990.0050.4680.293
10周龄空白组7170.794±32.5081.621±0.38151.136±18.22314.863±4.396
GTW组7160.035±26.3280.615±0.14964.256±4.22812.531±2.514
F值0.4477.6956.5123.725
P值0.655<0.0010.0880.247
8月龄空白组7181.820±54.8501.889±0.59659.349±10.91612.232±4.761
GTW组7173.888±34.2690.393±0.05867.279±6.33812.947±2.385
F值1.3553.1302.1361.214
P值0.7510.0020.1220.225
), ArticleFig(id=1322926392060551824, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表10, caption=

雷公藤多苷干预12周后不同年龄段大鼠血清T、FSH、LH、E2含量比较（）

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鼠龄组别nE2/（pg/mL）T/（ng/mL）FSH/（ng/mL）LH/（mIU/mL）
3周龄空白组7161.830±22.5842.433±0.64962.224±9.81614.487±3.296
GTW组7153.105±19.4620.557±0.21264.607±3.65912.095±1.593
F值2.86211.5136.7836.633
P值0.364<0.0010.5580.109
5周龄空白组7160.310±25.1131.395±0.59460.649±8.25914.546±2.426
GTW组7140.314±15.7260.610±0.13063.201±4.96712.824±3.354
F值2.1355.4022.6200.846
P值0.0990.0050.4680.293
10周龄空白组7170.794±32.5081.621±0.38151.136±18.22314.863±4.396
GTW组7160.035±26.3280.615±0.14964.256±4.22812.531±2.514
F值0.4477.6956.5123.725
P值0.655<0.0010.0880.247
8月龄空白组7181.820±54.8501.889±0.59659.349±10.91612.232±4.761
GTW组7173.888±34.2690.393±0.05867.279±6.33812.947±2.385
F值1.3553.1302.1361.214
P值0.7510.0020.1220.225
), ArticleFig(id=1322926392140243601, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n干预2周干预4周干预8周干预12周
密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）
3周龄空白组70.014±0.0240.000±0.0001.736±0.46313.234±2.2655.243±0.50623.484±3.3337.900±0.75520.620±2.036
GTW组70.021±0.0270.000±0.0001.029±0.35613.669±3.5714.443±0.57819.048±3.5834.579±1.0426.195±5.762
F值0.5370.0000.1132.1931.9830.0190.4214.556
P值0.5911.0000.0080.7900.0470.034<0.001<0.001
5周龄空白组71.664±0.23413.896±1.0834.879±0.27421.292±3.5276.529±0.55022.998±4.1588.971±0.69722.257±4.666
GTW组71.286±0.29413.951±1.1872.650±1.03418.769±2.6714.171±1.38217.832±8.5383.564±1.2821.622±1.942
F值0.0020.2895.6280.5262.2361.1742.5941.493
P值0.0210.930<0.0010.1570.0250.176<0.001<0.001
10周龄空白组76.214±0.50722.133±2.3076.950±0.38217.282±2.1529.071±0.49225.139±6.2438.514±0.86122.227±5.535
GTW组73.764±0.47116.412±7.7363.386±0.53013.736±7.4884.093±1.18115.156±3.6804.793±1.7389.088±7.267
F值0.0753.0951.1674.8327.3072.6193.7140.582
P值<0.0010.085<0.0010.252<0.0010.009<0.0010.003
8月龄空白组76.593±0.70920.832±3.1226.379±0.89726.429±4.1285.671±0.78829.434±1.8425.986±0.65622.745±3.206
GTW组73.336±0.95120.514±6.8043.136±0.96617.311±7.2962.879±0.67412.961±6.8732.500±1.0365.758±8.842
F值1.3816.4410.5715.6860.2545.8631.0803.006
P值<0.0010.912<0.0010.014<0.001<0.001<0.0010.003
), ArticleFig(id=1322926392228323986, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表11, caption=

雷公藤多苷干预2周、4周、8周、12周后不同年龄段大鼠精子密度及活率比较（）

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鼠龄组别n干预2周干预4周干预8周干预12周
密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）密度/（个×107/mL）活率/（%）
3周龄空白组70.014±0.0240.000±0.0001.736±0.46313.234±2.2655.243±0.50623.484±3.3337.900±0.75520.620±2.036
GTW组70.021±0.0270.000±0.0001.029±0.35613.669±3.5714.443±0.57819.048±3.5834.579±1.0426.195±5.762
F值0.5370.0000.1132.1931.9830.0190.4214.556
P值0.5911.0000.0080.7900.0470.034<0.001<0.001
5周龄空白组71.664±0.23413.896±1.0834.879±0.27421.292±3.5276.529±0.55022.998±4.1588.971±0.69722.257±4.666
GTW组71.286±0.29413.951±1.1872.650±1.03418.769±2.6714.171±1.38217.832±8.5383.564±1.2821.622±1.942
F值0.0020.2895.6280.5262.2361.1742.5941.493
P值0.0210.930<0.0010.1570.0250.176<0.001<0.001
10周龄空白组76.214±0.50722.133±2.3076.950±0.38217.282±2.1529.071±0.49225.139±6.2438.514±0.86122.227±5.535
GTW组73.764±0.47116.412±7.7363.386±0.53013.736±7.4884.093±1.18115.156±3.6804.793±1.7389.088±7.267
F值0.0753.0951.1674.8327.3072.6193.7140.582
P值<0.0010.085<0.0010.252<0.0010.009<0.0010.003
8月龄空白组76.593±0.70920.832±3.1226.379±0.89726.429±4.1285.671±0.78829.434±1.8425.986±0.65622.745±3.206
GTW组73.336±0.95120.514±6.8043.136±0.96617.311±7.2962.879±0.67412.961±6.8732.500±1.0365.758±8.842
F值1.3816.4410.5715.6860.2545.8631.0803.006
P值<0.0010.912<0.0010.014<0.001<0.001<0.0010.003
), ArticleFig(id=1322926392320598675, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n干预2周干预4周
精原细胞精母细胞精子细胞精原细胞精母细胞精子细胞
3周龄空白组70.236±0.0160.276±0.0240.488±0.0280.167±0.0140.220±0.0150.614±0.017
GTW组70.227±0.0320.269±0.0420.504±0.0440.179±0.0090.213±0.0160.608±0.022
F值5.9530.9051.1411.1070.0010.921
P值0.5190.7160.4340.0680.4290.588
5周龄空白组70.150±0.0100.212±0.0140.638±0.0230.141±0.0110.188±0.0080.671±0.016
GTW组70.171±0.0300.229±0.0550.600±0.0750.164±0.0270.194±0.0230.642±0.040
F值10.9026.2889.7092.4323.9634.395
P值0.1220.4610.2440.0580.5490.105
10周龄空白组70.145±0.0100.193±0.0090.662±0.0160.145±0.0120.194±0.0050.661±0.015
GTW组70.170±0.0260.202±0.0250.628±0.0400.195±0.0410.201±0.0200.605±0.057
F值1.8003.8891.2573.00313.4452.619
P值0.0390.4040.0620.0030.4660.009
8月龄空白组70.141±0.0130.192±0.0160.665±0.0190.153±0.0090.184±0.0140.662±0.018
GTW组70.155±0.0160.215±0.0120.631±0.0210.170±0.0230.216±0.0340.614±0.049
F值1.7250.3660.0688.0082.6831.163
P值0.0850.0130.0060.1150.0450.032
), ArticleFig(id=1322926392429650580, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表12, caption=

雷公藤多苷干预2周、4周后不同年龄段大鼠各级生精细胞比例（）

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鼠龄组别n干预2周干预4周
精原细胞精母细胞精子细胞精原细胞精母细胞精子细胞
3周龄空白组70.236±0.0160.276±0.0240.488±0.0280.167±0.0140.220±0.0150.614±0.017
GTW组70.227±0.0320.269±0.0420.504±0.0440.179±0.0090.213±0.0160.608±0.022
F值5.9530.9051.1411.1070.0010.921
P值0.5190.7160.4340.0680.4290.588
5周龄空白组70.150±0.0100.212±0.0140.638±0.0230.141±0.0110.188±0.0080.671±0.016
GTW组70.171±0.0300.229±0.0550.600±0.0750.164±0.0270.194±0.0230.642±0.040
F值10.9026.2889.7092.4323.9634.395
P值0.1220.4610.2440.0580.5490.105
10周龄空白组70.145±0.0100.193±0.0090.662±0.0160.145±0.0120.194±0.0050.661±0.015
GTW组70.170±0.0260.202±0.0250.628±0.0400.195±0.0410.201±0.0200.605±0.057
F值1.8003.8891.2573.00313.4452.619
P值0.0390.4040.0620.0030.4660.009
8月龄空白组70.141±0.0130.192±0.0160.665±0.0190.153±0.0090.184±0.0140.662±0.018
GTW组70.155±0.0160.215±0.0120.631±0.0210.170±0.0230.216±0.0340.614±0.049
F值1.7250.3660.0688.0082.6831.163
P值0.0850.0130.0060.1150.0450.032
), ArticleFig(id=1322926392521925269, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n干预8周干预12周
精原细胞精母细胞精子细胞精原细胞精母细胞精子细胞
3周龄空白组70.157±0.0160.191±0.0110.652±0.0260.140±0.0100.192±0.0110.668±0.015
GTW组70.193±0.0330.199±0.0430.613±0.0720.196±0.0580.209±0.0250.595±0.079
F值2.2547.4976.5827.9386.72212.181
P值0.0230.6310.2130.0420.1360.050
5周龄空白组70.150±0.0160.190±0.0140.660±0.0220.151±0.0110.198±0.0090.652±0.019
GTW组70.252±0.1670.247±0.0460.500±0.1970.223±0.0410.194±0.0620.583±0.010
F值4.1486.8074.2573.13011.7799.137
P值0.1350.0160.0550.0020.8690.121
10周龄空白组70.145±0.0120.194±0.0050.661±0.0150.155±0.0090.191±0.0220.655±0.021
GTW组70.195±0.0410.201±0.0200.605±0.0570.219±0.0300.241±0.0450.535±0.059
F值5.11913.44510.1425.9385.76110.327
P值0.0170.4660.0400.0010.0260.001
8月龄空白组70.126±0.0080.201±0.0170.673±0.0140.159±0.0200.192±0.0130.650±0.030
GTW组70.253±0.1340.255±0.0200.493±0.1420.256±0.1010.253±0.0280.491±0.116
F值9.3690.10710.9268.7342.0763.003
P值0.047<0.0010.0150.044<0.0010.003
), ArticleFig(id=1322926392622588566, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926378806551068, language=CN, label=表13, caption=

雷公藤多苷干预8周、12周后不同年龄段大鼠各级生精细胞比例（）

, figureFileSmall=null, figureFileBig=null, tableContent=
鼠龄组别n干预8周干预12周
精原细胞精母细胞精子细胞精原细胞精母细胞精子细胞
3周龄空白组70.157±0.0160.191±0.0110.652±0.0260.140±0.0100.192±0.0110.668±0.015
GTW组70.193±0.0330.199±0.0430.613±0.0720.196±0.0580.209±0.0250.595±0.079
F值2.2547.4976.5827.9386.72212.181
P值0.0230.6310.2130.0420.1360.050
5周龄空白组70.150±0.0160.190±0.0140.660±0.0220.151±0.0110.198±0.0090.652±0.019
GTW组70.252±0.1670.247±0.0460.500±0.1970.223±0.0410.194±0.0620.583±0.010
F值4.1486.8074.2573.13011.7799.137
P值0.1350.0160.0550.0020.8690.121
10周龄空白组70.145±0.0120.194±0.0050.661±0.0150.155±0.0090.191±0.0220.655±0.021
GTW组70.195±0.0410.201±0.0200.605±0.0570.219±0.0300.241±0.0450.535±0.059
F值5.11913.44510.1425.9385.76110.327
P值0.0170.4660.0400.0010.0260.001
8月龄空白组70.126±0.0080.201±0.0170.673±0.0140.159±0.0200.192±0.0130.650±0.030
GTW组70.253±0.1340.255±0.0200.493±0.1420.256±0.1010.253±0.0280.491±0.116
F值9.3690.10710.9268.7342.0763.003
P值0.047<0.0010.0150.044<0.0010.003
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雷公藤多苷对不同年龄段雄鼠毒性损伤的比较
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孙昭恒 1 , 丁樱 1 , 韩姗姗 1 , 徐闪闪 2 , 代彦林 2
中华中医药学刊 | 国家项目点击 2025,43(8): 101-110
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中华中医药学刊 |国家项目点击 2025 , 43 (8) : 101 -110
雷公藤多苷对不同年龄段雄鼠毒性损伤的比较
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孙昭恒1, 丁樱1 , 韩姗姗1, 徐闪闪2, 代彦林2
作者信息
  • 1.河南中医药大学儿科医学院，河南 郑州 450046
  • 2.河南中医药大学第一附属医院儿科医院，河南 郑州 450099
通讯作者:
丁樱（1951-），女，江苏南京人，主任医师、教授，国医大师，国家首批名中医，学士，研究方向：小儿肾脏病。E-mail：。
作者简介:

孙昭恒（1995-），女，河南郑州人，博士在读，研究方向：中医药防治小儿肾脏病。

Comparison of Glycosides of Leigongteng（Tripterygium wilfordii）on Toxic Damage in Male Rats of Different Ages
Zhaoheng SUN1, Ying DING1 , Shanshan HAN1, Shanshan XU2, Yanlin DAI2
Affiliations
  • 1.College of Pediatric Medicine，Henan University of Chinese Medicine，Zhengzhou 450046，Henan，China
  • 2.Pediatric Hospital，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450099，Henan，China
出版时间: 2025-08-10 doi: 10.13193/j.issn.1673-7717.2025.08.022
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摘要
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目的

比较雷公藤多苷（glycosides of tripterygium wilfordii，GTW）对不同年龄段雄鼠肝脏、血液、生殖系统的毒性损伤。

方法

选取3周龄、5周龄、10周龄、8月龄（相当于学龄前期、学龄期、青春期、成人期）SD雄鼠各56只，每个年龄段采用随机数字表法分为空白组和GTW 组，GTW 组给予12.5 mg/（kg·d）［相当于儿童2 mg/（kg·d）］GTW 悬浊液灌胃，空白组给予等量生理盐水灌胃，分别于2、4、8、12周每个年龄段各取7只空白组和GTW 组，计算肝脏、睾丸、附睾脏器指数；全自动血液细胞分析仪检测血常规指标；全自动干式生化分析仪检测肝功能指标；ELISA法检测睾酮、促卵泡生成素、促黄体生成素及雌二醇水平；HE染色法观察大鼠肝脏、睾丸、附睾组织病理改变；光学显微镜下计算精子密度和活率；ImajeJ软件统计睾丸生精小管内精原细胞、精母细胞、精子细胞的比例。

结果

从肝脏系统来看，各年龄段大鼠在GTW干预期间未出现肝脏指数明显升高，第4周、第8周出现丙氨酸氨基转移酶、天冬氨酸氨基转移酶升高（P<0.05），第12周恢复；肝脏病理形态显示肝脏损伤程度随灌胃时间而加重，而各年龄段之间的损伤程度未见明显差异。从血液系统来看，血小板减少（P<0.05）最早出现，第12周恢复；5周龄、10周龄大鼠第4周出现白细胞减少（P<0.05），第12周恢复；血红蛋白减少（P<0.05）最晚出现，除3周龄大鼠外均在第12周恢复。从生殖系统来看，5周龄、8月龄大鼠于第4周出现睾酮下降（P<0.05），而后所有大鼠睾酮均下降（P<0.05）；除3周龄大鼠外其余均在第2周出现精子密度下降（P<0.05），第4周8月龄大鼠最早出现精子密度、活率均下降（P<0.05）；第2周8月龄大鼠最早出现精子细胞比例下降（P<0.05）；睾丸、附睾病理均显示8月龄大鼠损伤较重。

结论

①GTW 对不同年龄段大鼠的肝脏损伤无明显差异，但随用药时间而加重；②GTW 对血液系统的毒性表现为血常规指标下降的不一致性，且幼鼠较成鼠更不耐受GTW 造成的血液损伤。③相对幼鼠，成鼠对GTW 的生殖毒性更为敏感。

雷公藤多苷  /  毒性  /  损伤  /  不同年龄段  /  比较
Objective

To compare the toxic effects of glycosides of Leigongteng（Tripterygium wilfordii）（GTW）on liver，blood and reproductive system in male rats of different ages.

Methods

Fifty-six male Sprague-Dawley（SD）rats aged 3，5 and 10 weeks and 8 months（equivalent to pre-school age，school age，adolescence and adulthood）were selected.The each age group was divided into control group and GTW group by random number table method.The GTW group was given 12.5 mg/（kg·d）［equivalent to2 mg/（kg·d）for children］GTW suspension，and the control group was given the same amount of normal saline.Seven rats in each age group were taken from the control group and GTW group at 2，4，8 and 12 weeks，respectively，and the organ indexes of liver，testis and epididymis were calculated.Blood routine indexes were detected by automatic blood cell analyzer.Liver function indexes were detected by automatic dry biochemical analyzer.The serum levels of testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH）and estradiol（E2）were detected by ELISA.The histopathological changes of liver，testis and epididymis were observed by HE staining.Sperm density and viability were calculated under light microscope.ImajeJ software counted the proportion of spermatogonia，spermatocytes and spermatids in the seminiferous tubules of the testis.

Results

From the perspective of the liver system，there was no significant increase in liver index in rats of all age groups during GTW intervention.Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）increased at the 4th and 8th week（P<0.05），and recovered at the 12th week.The pathological morphology of the liver showed that the degree of liver damage increases with the time of gastric lavage，and there was no significant difference between different age groups.From the perspective of the blood system，a decrease in PLT（P<0.05）appeared earliest and recovered by the 12th week.The rats aged 5 and 10 weeks showed a decrease in white blood cell（WBC）at 4th week（P<0.05）and recovered at 12th week.The decrease in hemoglobin（HB）（P<0.05）appeared the latest and all except for 3-week-old rats recovered at 12th week.From the perspective of the reproductive system，5-week-old and 8-month-old rats showed a decrease in T at the 4th week（P<0.05），followed by a decrease in T in all rats（P<0.05）.Except for 3-week-old rats，all other rats showed a decrease in sperm density in the second week（P<0.05），while 8-month-old rats showed the earliest decrease in sperm density and viability in the 4th week（P<0.05）.In the second week，8-month-old rats showed a decrease in the proportion of sperm cells at the earliest stage（P<0.05）.Pathology of the testes and epididymis both showed severe damage in 8-month-old rats.

Conclusion

①There was no significant difference in liver damage caused by GTW in rats of different age groups，but it worsened with medication time.②The toxicity of GTW to the blood system is manifested by inconsistent decreases in blood routine indicators，and young rats are more intolerant to blood damage caused by GTW than adult rats.③Compared to young rats，adult rats are more sensitive to the reproductive toxicity of GTW.

glycosides of Leigongteng（Tripterygium wilfordii）  /  toxicity  /  damage  /  different age groups  /  comparison
孙昭恒, 丁樱, 韩姗姗, 徐闪闪, 代彦林. 雷公藤多苷对不同年龄段雄鼠毒性损伤的比较. 中华中医药学刊, 2025 , 43 (8) : 101 -110 . DOI: 10.13193/j.issn.1673-7717.2025.08.022
Zhaoheng SUN, Ying DING, Shanshan HAN, Shanshan XU, Yanlin DAI. Comparison of Glycosides of Leigongteng（Tripterygium wilfordii）on Toxic Damage in Male Rats of Different Ages[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (8) : 101 -110 . DOI: 10.13193/j.issn.1673-7717.2025.08.022
正文
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雷公藤多苷（glycosides of tripterygium wilfordii，GTW）是具有我国民族自主知识产权、临床使用最多也是疗效最可靠的免疫抑制类中成药，具有抗炎、抑制细胞免疫和体液免疫、抗肿瘤等药理作用[1]，被列入类风湿关节炎[2]、狼疮肾炎[3]、紫癜性肾炎[4]等多种免疫疾病的用药指南。课题组承担的“十二五”国家科技支撑项目也发现GTW 可有效降低紫癜性肾炎患儿蛋白尿水平[5]，然而，研究表明GTW 对肝脏、血液、生殖系统具有毒性作用[6]，使得GTW 在儿童群体中的应用备受争议。然儿童定义为0～18岁以内的所有儿童，年龄跨度大，不同年龄段儿童的器官功能较成人相比各有差异，对GTW 的耐受性也各不相同，本研究按照儿童学龄前期、学龄期、青春期、成人期将SD鼠分为4个年龄段组（3周龄、5周龄、10周龄、8月龄），采用GTW 临床剂量（折算为大鼠灌胃剂量）干预2、4、8、12周后，综合肝脏、生殖、血液毒性观察GTW 对不同年龄段大鼠毒性损伤的差异性，为临床儿科安全合理用药提供指导。
1　材料
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1.1　动物
3周龄、5周龄、10周龄、8月龄Sprague-Dawley雄性大鼠各56只，均购自北京华府康生物科技股份有限公司［SCXK（京）2019-0008］，饲养于河南中医药大学动物实验中心［SYXK（豫）2020-0004］。饲养环境温度18～24℃，湿度40%～60%，明暗交替时间为12 h，自由饮食。本实验获得河南中医药大学实验动物伦理委员会批准（伦理号：DWLL202209001）。所有实验程序遵循河南中医药大学实验动物保护和应用条例。
1.2　药物
GTW 购自江苏美通制药有限公司（批号：220601，规格：10 mg/片×50片）。
1.3　主要试剂及仪器
睾酮（testosterone，T）、促卵泡生成素（follicle stimulating hormone，FSH）、促黄体生成素（luteinizing hormone，LH）及雌二醇（estradiol2，E2）ELISA试剂盒购自武汉伊莱瑞特生物科技股份有限公司 （生产批号分别为 NM22TLD29764、NM058T8P4862、NM07B4887989及NM0328041734）；肝功能冻干试剂盒购自天津微纳芯科技有限公司（生产批号：Z30750）。
迈瑞兽用全自动血液细胞分析仪（型号：BC-2800vet）；瑞士TECAN帝肯酶标仪（型号：Infinite F50）；全自动干式生化分析仪（型号：Celercare M5）。
2　方法
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2.1　分组及给药
将3周龄、5周龄、10周龄、8月龄大鼠随机分为空白组和GTW 组，每组28只，GTW 组给予12.5 mg/（kg·d）［相当于儿童2 mg/（kg·d）］GTW 悬浊液灌胃，空白组给予等量生理盐水灌胃。
2.2　样本采集
于灌胃2、4、8、12周每个年龄段各取7只空白组和7只GTW 组大鼠，禁食不禁水12 h后称取体质量，腹腔注射40 mg/kg戊巴比妥钠麻醉后腹主动脉取血，1管放置于抗凝管并晃动均匀，剩余血液4℃静置30 min后，3000 r/min（离心半径10 cm）离心15 min，吸取上层血清，-80℃冻存。
于冰上迅速分离肝脏、右侧睾丸、右侧附睾，称取质量后置于4%多聚甲醛中固定。左侧附睾用于精子密度及活力检测。
2.3　指标检测
2.3.1　肝脏、睾丸、附睾脏器指数
吸水纸拭干脏器表面血液，并置于精密称重仪上称重记录每个脏器的质量，最后计算各脏器指数。脏器指数＝脏器质量/大鼠体质量×100%。
2.3.2　血常规、肝功能
取抗凝管中血液2 mL并通过全自动血液细胞分析仪检测白细胞（white blood cell，WBC）、血红蛋白（hemoglobin，HB）、血小板（platelet，PLT）等血常规指标，取血清2 mL并通过全自动干式生化分析仪检测丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）等肝功能指标。
2.3.3　血清T、FSH、LH、E2含量
严格按照ELISA试剂盒说明书进行操作。在450 nm波长下，读取吸光度值。
2.3.4　肝脏、睾丸、附睾病理学形态
肝脏、睾丸、附睾组织经4%多聚甲醛固定48 h后，常规石蜡包埋，连续切片（厚2 μm）。石蜡切片经二甲苯脱蜡、梯度乙醇水化，苏木素-伊红染色后，再经梯度乙醇、二甲苯脱水透明后，中性树脂封片。光学显微镜观察肝脏、睾丸、附睾组织的病理形态。
2.3.5　精子密度及活率
取左侧附睾尾部（去除脂肪、筋膜）放入盛有2 mL预热生理盐水的EP管中，用剪刀将附睾组织剪碎（约80下），并用移液器吹打数次，37℃温浴5 min让精子充分游离，用70μm滤网过滤后制成精子混悬液。吸取20 μL精子混悬液滴于载玻片上，于400倍光学显微镜下随机观察3个视野，记录运动的精子数和总精子数，运动的精子/总精子数×100%为精子活率。另取1 mL滤液加4 m L 5%NaHCO3溶液固定精子，于细胞计数板上计算精子密度。
2.3.6　睾丸生精细胞计数
将睾丸切片于光学显微镜下放大100倍，随机选取5个视野取图，使用ImajeJ软件统计生精小管内精原细胞、精母细胞、精子细胞的比例，计算平均值并进行分析。
2.4　统计分析
使用SPSS 26.0统计学软件进行统计分析，计量资料以均数±标准差（）来表示，正态分布的两组间比较采用两独立样本t检验，若方差不齐使用t′检验，非正态分布时采用Wilcoxon秩和检验，P<0.05为差异具有统计学意义。
3　结果
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3.1　GTW 对不同年龄段大鼠肝脏、睾丸、附睾脏器指数的影响
对GTW干预4周后各年龄段大鼠脏器指数进行分析，发现3周龄大鼠睾丸、附睾脏器指数均降低（P<0.05），如表1所示。
对GTW干预8周后各年龄段大鼠脏器指数进行分析，发现5周龄大鼠睾丸指数降低（P<0.05），10周龄、8月龄大鼠附睾指数降低（P<0.05）。
对GTW干预12周后各年龄段大鼠脏器指数进行分析，发现5周龄、8月龄大鼠睾丸、附睾脏器指数均降低（P<0.05）；10周龄大鼠附睾指数降低（P<0.05），如表2所示。
3.2　GTW 对不同年龄段大鼠血常规、肝功能的影响
对GTW干预2周后各年龄段大鼠血常规、肝功能进行分析，发现5周龄、10周龄、8月龄大鼠PLT降低（P<0.05），如表3所示。
对GTW干预4周后各年龄段大鼠血常规、肝功能进行分析，发现5周龄、10周龄大鼠WBC降低（P<0.05）；3周龄、5周龄、10周龄、8月龄大鼠全部出现PLT降低（P<0.05）；3周龄、8月龄大鼠ALT、AST升高（P<0.05）；5周龄、10周龄大鼠ALT升高（P<0.05），如表4所示。
对GTW干预8周后各年龄段大鼠血常规、肝功能进行分析，发现10周龄大鼠WBC降低（P<0.05）；3周龄、5周龄大鼠HB降低（P<0.05）；5周龄、8月龄大鼠PLT降低（P<0.05）；3周龄、5周龄、10周龄大鼠ALT升高（P<0.05），而8月龄大鼠ALT、AST均升高（P<0.05），如表5所示。
对GTW干预12周后各年龄段大鼠血常规、肝功能进行分析，发现3周龄大鼠HB降低（P<0.05）；8月龄大鼠AST升高（P<0.05），如表6所示。
3.3　GTW 对不同年龄段大鼠血清T、FSH、LH、E2含量的比较
对GTW干预2周后各年龄段大鼠血清T、FSH、LH、E2含量进行分析，发现各项指标差异无统计学意义，如表7所示。
对GTW干预4周后各年龄段大鼠血清T、FSH、LH、E2含量进行分析，发现5周龄、8月龄大鼠T含量降低（P<0.05），其余指标差异无统计学意义，如表8所示。
对GTW干预8周后各年龄段大鼠血清T、FSH、LH、E2含量进行分析，发现3周龄、5周龄、10周龄、8月龄大鼠T含量全部降低（P<0.05），其余指标差异无统计学意义，如表9所示。
对GTW干预12周后各年龄段大鼠血清T、FSH、LH、E2含量进行分析，发现所有年龄段大鼠T含量全部降低（P<0.05），其余指标差异无统计学意义，如表10所示。
3.4　GTW 对不同年龄段大鼠肝脏、睾丸、附睾病理学形态的影响
3.4.1　GTW 对不同年龄段大鼠肝脏病理学形态的影响
空白组小鼠肝脏的肝细胞结构清晰、呈多边形，肝索呈放射状排列，胞质呈紫红色，细胞核大而圆，处于细胞中央；GTW干预2周后，可见各年龄段大鼠肝细胞轻度肿胀、变性，肝窦变窄；GTW干预4周后，可见各年龄段大鼠肝细胞水肿、变性，肝小叶中央静脉及汇管区充满红细胞，肝窦扩张充血，可见点状坏死，见插页ⅩⅩⅧ图1。
GTW干预8周后，各年龄段大鼠出现胞质疏松化，有灶状坏死，伴炎细胞浸润；GTW干预12周后，各年龄段大鼠出现肝细胞排列紊乱，肝细胞变性、模糊，有灶状、片状坏死，伴大量炎细胞浸润，肝板破坏，见插页ⅩⅩⅨ图2。
3.4.2　GTW 对不同年龄段大鼠睾丸病理学形态的影响
空白组大鼠睾丸组织结构清晰，管腔完整，各级生精细胞排列规则，间隙紧密。GTW干预2周后，3周龄、5周龄、10周龄大鼠生精小管形态尚饱满，各级生精细胞排列尚规则，数量无明显变化；8月龄大鼠上皮变薄，各级生精细胞排列紊乱，精子细胞数量减少。GTW干预4周后，3周龄、5周龄、10周龄大鼠上皮变薄，生精细胞排列稍紊乱；8月龄大鼠上皮变薄，生精细胞数量及层次减少，间隙增大，分布散乱，见插页ⅩⅩⅩ图3。
GTW干预8周后，3周龄、5周龄、10周龄大鼠生精细胞排列疏松，层次不清；8月龄大鼠生精小管基膜破损，形态萎缩，腔隙增宽，生精细胞脱失，可见空泡化。GTW干预12周后，3周龄、5周龄、10周龄大鼠管腔上皮萎缩，各级生精细胞排列散乱，可见空泡化；8月龄大鼠睾丸结构严重损伤，生精细胞大量脱失，出现空腔型生精小管，见插页ⅩⅩⅪ图4。
3.4.3　GTW 对不同年龄段大鼠附睾病理学形态的影响
空白组大鼠附睾管腔充盈，上皮呈假复层柱形排列，间质胶原丰富，管腔内可见大量线性精子。GTW干预2周后，3周龄大鼠管腔体积基本正常，上皮细胞部分尚规则、整齐，腔缘整齐光滑，间质稍水肿；5周龄、10周龄大鼠管腔体积缩小，精子脱落聚集成团，间质水肿；8月龄大鼠管腔内精子减少，间质内充大量粉红色液体。GTW干预4周后，3周龄大鼠管腔体积缩小，管腔内精子脱落聚集成团；5周龄、10周龄大鼠管腔内精子减少，部分管腔空虚；8月龄大鼠管腔上皮细胞排列紊乱，管腔内精子大量减少，偶见管腔断裂，见插页ⅩⅩⅫ图5。
GTW干预8周后，3周龄、5周龄、10周龄大鼠管腔体积缩小，精子减少，部分管腔空虚，内充粉红色液体；8月龄大鼠管腔上皮细胞排列紊乱，精子大量减少，大量管腔空虚，部分管腔断裂；GTW干预12周后，3周龄、5周龄、10周龄大鼠管腔体积缩小，精子大量减少，脱落聚集成团，部分管腔空虚；8月龄大鼠管腔上皮细胞排列紊乱，管腔内精子极少，大量管腔空虚，部分管腔断裂，见插页ⅩⅩⅩⅢ图6。
3.5　GTW 对不同年龄段大鼠精子密度及活率的影响
对GTW干预2周、4周、8周、12周后各年龄段大鼠精子密度及活率进行分析，发现GTW干预2周后5周龄、10周龄、8月龄大鼠精子密度降低（P<0.05）；GTW干预4周后3周龄、5周龄、10周龄大鼠精子密度降低（P<0.05），8月龄大鼠精子密度、活率均降低（P<0.05）；GTW干预8周后5周龄大鼠精子密度降低（P<0.05），3周龄、10周龄、8月龄大鼠精子密度、活率均降低（P<0.05）；GTW干预12周后所有年龄段大鼠精子密度、活率全部降低（P<0.05），如表11所示。
3.6　GTW 对不同年龄段大鼠睾丸各级生精细胞比例的影响
对GTW干预2周、4周后各年龄段大鼠睾丸各级生精细胞的比例进行分析，发现GTW干预2周后10周龄大鼠精原细胞比例升高（P<0.05）；8月龄大鼠精母细胞比例升高，精子细胞比例降低（P<0.05）。GTW干预4周后10周龄大鼠精原细胞比例升高，精子细胞比例降低（P<0.05）；8月龄大鼠精母细胞比例升高，精子细胞比例降低（P<0.05），如表12所示。
对GTW干预8周、12周后各年龄段大鼠睾丸各级生精细胞的比例进行分析，发现GTW干预8周后3周龄大鼠精原细胞比例升高（P<0.05）；5周龄大鼠精母细胞比例升高（P<0.05）；10周龄大鼠精原细胞比例升高，精子细胞比例降低（P<0.05）；8月龄大鼠精原细胞、精母细胞比例升高，精子细胞比例降低（P<0.05）。GTW干预12周后3周龄、5周龄大鼠精原细胞比例升高（P<0.05）；10周龄、8月龄大鼠精原细胞、精母细胞比例升高，精子细胞比例降低（P<0.05），如表13所示。
4　讨论
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GTW 在儿童紫癜性肾炎、狼疮肾炎、IgA肾病等肾脏疾病中应用广泛[7]，然而其安全性尚存争议。研究表明[8]GTW 对于儿童的不良反应近期以血液、肝脏系统为主，远期以生殖系统为主。然而不同年龄段机体生长发育程度不同，导致靶器官对毒性的应答存在差异[9]，这种差异正是当前GTW 毒性相关研究所缺乏的。基于此，本研究以不同年龄段大鼠为对象，采用儿童紫癜性肾炎的临床剂量[10]进行折算，选取肝脏系统、血液系统、生殖系统毒性变化作为评价指标，旨在明确GTW 对不同年龄段雄鼠毒性损伤的差异性。
从肝脏系统来看，各年龄段大鼠在GTW干预期间未出现肝脏指数明显升高，且均于第4周、第8周出现ALT、AST升高（P<0.05），第12周恢复；同时，肝脏病理形态表明各年龄段大鼠在灌胃期间出现不同程度的肝脏损伤，其程度随灌胃时间而加重，而各年龄段之间损伤程度未见明显差异。李红刚等[11]整理了使用GTW 的683例病人，发现110例出现肝损伤，年龄跨度为3～70岁，提示GTW 的肝毒性损伤与患者年龄无明显相关性，与本研究结果一致。同时，本研究发现在未进行其他干预的情况下，大鼠肝酶可恢复，这可能与药物耐受性有关，例如，异烟肼治疗潜伏性结核病导致约20%的患者ALT轻度升高，然而即使在继续使用异烟肼的情况下，许多患者产生了耐受性并出现了ALT水平的下降[12]。也可能与肝脏的自我修复能力有关，有研究[13]显示在肝脏无菌性损伤模型中，恒定自然杀伤T细胞分泌白细胞介素-4，将炎症单核细胞转化为修复表型，诱导肝细胞再生，然而，若反复刺激持续存在，招募的先天免疫细胞可能最终导致损伤而不是修复，这也导致各年龄段大鼠肝脏病理损伤程度随灌胃时间变长而加重。值得注意的是，药物性肝损伤有时会表现为轻度的肝酶升高，即肝酶升高程度不能简单等同于肝脏损伤程度[14]。研究表明，GTW 导致的肝脏损伤主要与雷公藤甲素诱导的氧化应激相关：高水平活性氧和活性氮抑制细胞膜上的钠泵、ATP酶和钙泵活性，导致线粒体膜电位降低和凋亡因子Caspase-3的释放，造成肝细胞损伤[15]。也有体外实验证明，雷公藤甲素可诱导永生化人肝细胞L02产生细胞毒作用，导致线粒体功能障碍，增加自噬通量[16]。同时，GTW 中的雷公藤红素作为细胞色素P450酶的抑制剂，可加重雷公藤甲素的肝毒性，这也解释了为何GTW 肝脏毒性与剂量密切相关。总之，GTW 中的雷公藤红素和雷公藤甲素通过降低细胞存活率、增强细胞应激、降低基质金属蛋白酶、增加乳酸脱氢酶和活性氧水平，损伤大鼠肝细胞[17-18]
从血液系统来看，各年龄段大鼠首先出现PLT减少（P<0.05），第12周在未停药情况下PLT均可恢复；5周龄、10周龄大鼠于干预4周出现WBC减少（P<0.05），同样于第12周恢复；HB减少（P<0.05）最晚出现，除3周龄大鼠其余均在第12周恢复。GTW 的血液毒性表现为血常规指标下降的不一致性，有动物研究[19]发现小剂量雷公藤可引起WBC减少，进一步增加剂量又引起RBC减少，同样证实了这一点。本实验可以看出，GTW干预期间3周龄、5周龄、10周龄大鼠均出现不同程度的WBC减少，而8月龄大鼠未曾出现，且截至第12周只有3周龄大鼠HB未恢复，表明幼鼠较成鼠更不耐受GTW造成的血液损伤，有研究分析了GTW 用药者发生的血液系统不良事件，发现儿童HB减少率明显高于成人[20]，另有研究观察应用雷公藤制剂治疗类风湿关节炎的271例患者，发现年龄越大血液系统不良反应发生率越小，可能与机体的内分泌功能及免疫功能下降有关[21]。而GTW 的血液毒性，可能与异常免疫损伤造血干（祖）细胞相关：有学者发现GTW 所致血液毒性患者的骨髓T淋巴细胞增多，CD8+T淋巴细胞集落增高，CD4+T淋巴细胞减少，CD4+T/CD8+T降低，T淋巴细胞处于激活状态[22]，表明机体出现免疫紊乱，另有研究表明GTW 中的雷公藤红素可以显著调节成年小鼠外周血、骨髓、脾和腹腔中的干细胞、祖细胞和完全分化细胞群的数量，其潜在机制与核转录因子-κB信号通路有关[23]。
从生殖系统来看，5周龄、8月龄大鼠于第4周出现T下降（P<0.05），而第8周、第12周所有大鼠T均下降（P<0.05）；从精子密度、活率看，GTW 灌胃2周时除3周龄大鼠外，其余均出现精子密度下降（P<0.05），而GTW 灌胃4周时8月龄大鼠精子密度、活率均下降（P<0.05）；从各级生精细胞比例来看，8月龄大鼠在灌胃2周即出现精子细胞比例下降（P<0.05），结合睾丸、附睾病理变化，可发现相对幼鼠，GTW 对成鼠的生殖损伤更为敏感，这种原因可能与GTW 的生殖损伤机制相关。正常情况下，精原细胞通过支持细胞、间质细胞及其他多种体细胞的共同调控，逐渐分化为初级精母细胞、次级精母细胞、精子细胞和精子[24]，而GTW 的生殖毒性涉及多种机制，首先，GTW 及其主要成分可通过多种途径诱发睾丸内细胞凋亡，例如雷公藤甲素可激活大鼠睾丸间质细胞线粒体的凋亡通路，诱导的大鼠睾丸间质细胞凋亡[25-26]，也可通过激活Caspase家族的下游通路来诱导生精细胞[27]凋亡，尽管细胞凋亡在精原干细胞、睾丸支持细胞、间质细胞及精母细胞中均会出现[28]，但不同生精细胞对于GTW 毒性的敏感性不同，修晓宇[29]采用γ-H2AX免疫组化染色区分不同阶段初级精母细胞，发现细线期初级精母细胞可能是对雷公藤甲素毒性最敏感靶细胞，本研究也发现，GTW干预后各周龄大鼠的各级生精细胞出现精子细胞比例降低、精原细胞比例升高的现象，同样说明了GTW 对于生精细胞毒性的差异性。幼鼠性腺发育尚未完全，睾丸生精细胞多为上游未分化的精原细胞，可能造成GTW毒性的敏感性低于成熟大鼠。其次，GTW 还可通过抑制琥珀酸脱氢酶、酸性磷酸酶、乳酸脱氢酶和腺苷三磷酸酶等睾丸组织相关酶的活性[30-31]以及降低抑制素B[32]、T[33]等睾丸相关激素的分泌，从而抑制大鼠生精能力、生精过程和精子运动，降低精子数量和活力，而幼鼠自身生精能力尚不完全，少见成熟精子，因此受GTW 生殖毒性的影响较小。然而，本研究结果表明，随着幼鼠年龄的增长和GTW干预时间增加，幼鼠仍会出现精子细胞比例、精子数量/活力降低等生殖损伤表现，提示临床仍应注意GTW 疗程和剂量的把控。
本研究首次探究临床剂量的GTW 对不同年龄段大鼠肝脏、血液、生殖系统损伤的差异性，为GTW 针对不同年龄段的安全应用提供了一定参考价值。然而，本研究每组样本量较少，评价指标不够全面，且没有将病理状态的影响考虑在内，后期拟在扩大样本量的同时，引入病症结合模型，全面评价各系统损伤变化。
基金
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  • 国家自然科学基金项目(82205187; 82305311)
  • 河南省中医学“双一流”创建科学研究专项(HSRP-DFCTCM-2023-1-01)
  • 河南中医药大学研究生科研创新项目(2022KYCX018)
文献
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2025年第43卷第8期
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doi: 10.13193/j.issn.1673-7717.2025.08.022
  • 首发时间：2026-10-30
  • 出版时间：2025-08-10
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基金
国家自然科学基金项目(82205187; 82305311)
河南省中医学“双一流”创建科学研究专项(HSRP-DFCTCM-2023-1-01)
河南中医药大学研究生科研创新项目(2022KYCX018)
作者信息
    1.河南中医药大学儿科医学院，河南 郑州 450046
    2.河南中医药大学第一附属医院儿科医院，河南 郑州 450099

通讯作者:

丁樱（1951-），女，江苏南京人，主任医师、教授，国医大师，国家首批名中医，学士，研究方向：小儿肾脏病。E-mail：。
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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2025.08.022
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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