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Article(id=1324078139311260252, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202509470, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1758902400000, receivedDateStr=2025-09-27, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793614428593, onlineDateStr=2026-11-02, pubDate=1770652800000, pubDateStr=2026-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793614428593, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793614428593, creator=13701087609, updateTime=1793614428593, updator=13701087609, issue=Issue{id=1324078037817504735, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='3', pageStart='385', pageEnd='576', issueExtLink='null', onlineDate='null', pubDate='1770652800000', pubDateStr='2026-02-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793614404396, creator='13701087609', updateTime=1793614474144, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324078330420527919, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324078330420527920, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324078037817504735, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=519, endPage=524, ext={EN=ArticleExt(id=1324078140955427421, articleId=1324078139311260252, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Protective effect of resveratrol on reproductive toxicity induced by nano titanium dioxide in male mice, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate whether resveratrol has a protective effect against reproductive toxicity induced by nano titanium dioxide (Nano-TiO2) in male mice.

Methods

A total of 50 healthy male ICR mice were randomly divided into the control group, Nano-TiO2 group, and mixed groups with Nano-TiO2 plus low-, medium-, and high-dose resveratrol. After 28 days of continuous gavage, epididymal tissue was collected for semen quality measurement, and testicular tissue was used to evaluate pathological changes, testicular tissue-specific functional enzymes, and oxidative damage related indicators.

Results

After exposure to Nano-TiO2, the testicular and epididymal coefficients of mice decreased significantly (P<0.05), sperm density and vitality decreased significantly (P<0.05), sperm deformity rate increased significantly (P<0.05), the number of spermatogenic cells in the testicular seminiferous tubules decreased, and the Johnsen score decreased significantly (P<0.05).The activities of acid phosphatase, alkaline phosphatase, lactate dehydrogenase, glutathione peroxidase (GPx), superoxide dismutase, catalase, and reduced glutathione all decreased significantly (P<0.05), and the level of malondialdehyde increased significantly (P<0.05). After intervention with resveratrol, compared with the Nano-TiO2 exposed group, the testicular and epididymal coefficients increased, semen quality and pathological tissue damage improved significantly (P<0.05), acid phosphatase and lactate dehydrogenase activities were significantly increased (P<0.05), and malondialdehyde levels in testicular tissue decreased significantly, while superoxide dismutase, glutathione peroxidase, and catalase activities increased significantly (P<0.05). After correlation analysis, it was found that there was a significant correlation between antioxidant enzymes and malondialdehyde and the indicators of semen quality and testicular function enzymes.

Conclusion

Resveratrol has a protective effect against reproductive toxicity induced by Nano-TiO2 in male mice.

, authors=Hong-mei AN, Li-hong ZHANG, Jia-le MIAO, Jing-zhuo ZHANG, Ai-man SONG, WULIKEBAIKE-Maihemuti, Xian-feng CAO, Yong-chang WEN, Qi LI, Rui-ying YAN, Cai-jin REN, Qian-jiang BAO, Jia-yu WANG, Yu-hang LEI, authorsList=Hong-mei AN, Li-hong ZHANG, Jia-le MIAO, Jing-zhuo ZHANG, Ai-man SONG, WULIKEBAIKE-Maihemuti, Xian-feng CAO, Yong-chang WEN, Qi LI, Rui-ying YAN, Cai-jin REN, Qian-jiang BAO, Jia-yu WANG, Yu-hang LEI, authorCompany=null, correspAuthors=Hong-mei AN, 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=1324078143597838969, articleId=1324078139311260252, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=白藜芦醇对纳米二氧化钛诱导的雄性小鼠生殖毒性的保护作用, columnId=1228016572288135432, journalTitle=现代预防医学, columnName=实验技术及其应用, runingTitle=null, highlight=null, articleAbstract=
目的

探究白藜芦醇是否对纳米二氧化钛(nano titanium dioxide，Nano-TiO2)诱导的雄性小鼠生殖毒性具有保护作用。

方法

50只健康雄性ICR小鼠随机分为对照组、Nano-TiO2组、Nano-TiO2和低中高剂量白藜芦醇混合组。连续灌胃28 d后，取附睾组织进行精液品质测定，并使用睾丸组织评估病理变化、睾丸组织特异性功能酶以及氧化损伤相关指标。

结果

Nano-TiO2灌胃处理后小鼠睾丸系数和附睾系数均下降，精子密度、活力显著降低(P<0.05)，精子畸形率显著升高(P<0.05)，睾丸生精小管中生精细胞数量减少，Johnsen评分明显下降(P<0.05)；酸性磷酸酶、碱性磷酸酶、乳酸脱氢酶活性以及谷胱甘肽过氧化物酶、超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽均显著下降(P<0.05)；丙二醛水平显著升高(P<0.05)。白藜芦醇干预后，与Nano-TiO2组相比，睾丸系数和附睾系数回升，精液品质和病理组织损伤明显好转(P<0.05)，酸性磷酸酶和乳酸脱氢酶活性均显著提高(P<0.05)，同时睾丸组织中丙二醛水平显著下降、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶活性明显上升(P<0.05)。经过相关性分析，抗氧化酶以及丙二醛与精液品质和睾丸功能酶之间存在显著关联性。

结论

白藜芦醇对Nano-TiO2诱导的雄性小鼠生殖毒性具有保护作用。

, authors=安红梅, 张理弘, 苗加乐, 张婧卓, 宋艾蔓, 吾力克拜克·买合木提, 曹先峰, 温永昌, 李琦, 闫瑞英, 任财进, 包乾江, 王佳煜, 雷宇航, authorsList=安红梅, 张理弘, 苗加乐, 张婧卓, 宋艾蔓, 吾力克拜克·买合木提, 曹先峰, 温永昌, 李琦, 闫瑞英, 任财进, 包乾江, 王佳煜, 雷宇航, authorCompany=null, correspAuthors=安红梅, authorNote=

安红梅(1994—)，女，硕士，讲师，研究方向：生殖毒理学与分子流行病学

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安红梅，E-mail:
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安红梅(1994—)，女，硕士，讲师，研究方向：生殖毒理学与分子流行病学

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安红梅(1994—)，女，硕士，讲师，研究方向：生殖毒理学与分子流行病学

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Protective effects of resveratrol on zearalenone-induced liver oxidative damage and inflammation in mice[J]. China Animal Husbandry & Veterinary Medicine, 2021, 48(11): 4254-4261. (In Chinese), articleTitle=Protective effects of resveratrol on zearalenone-induced liver oxidative damage and inflammation in mice, refAbstract=null), Reference(id=1324078159091598081, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, doi=null, pmid=null, pmcid=null, year=2021, volume=10, issue=2, pageStart=217, pageEnd=null, url=null, language=null, rfNumber=[28], rfOrder=33, authorNames=Ferramosca A, Lorenzetti S, Di Giacomo M, journalName=Antioxidants, refType=null, unstructuredReference=Ferramosca A, Lorenzetti S, Di Giacomo M, et al. Modulation of human sperm mitochondrial respiration efficiency by plant polyphenols[J].Antioxidants, 2021, 10(2): 217., articleTitle=Modulation of human sperm mitochondrial respiration efficiency by plant polyphenols, refAbstract=null), Reference(id=1324078159188067074, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, doi=null, pmid=null, pmcid=null, year=2023, volume=32, issue=9, pageStart=5, pageEnd=9, url=null, language=null, rfNumber=[29], rfOrder=34, authorNames=石拴霞, 王纪田, 魏璐晓, journalName=中国性科学, refType=null, unstructuredReference=石拴霞，王纪田，魏璐晓，等.白藜芦醇治疗精子线粒体损伤导致的男性不育的作用机制研究进展[J].中国性科学，2023，32（9）：5-9., articleTitle=白藜芦醇治疗精子线粒体损伤导致的男性不育的作用机制研究进展, refAbstract=null), Reference(id=1324078159259370243, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, doi=null, pmid=null, pmcid=null, year=2023, volume=32, issue=9, pageStart=5, pageEnd=9, url=null, language=null, rfNumber=[29], rfOrder=35, authorNames=Shi SX, Wang JT, Wei LX, journalName=Chinese Journal of Human Sexuality, refType=null, unstructuredReference=Shi SX, Wang JT, Wei LX, et al. Research progress on the mechanism of resveratrol in the treatment of male infertility caused by sperm mitochondrial damage[J]. Chinese Journal of Human Sexuality, 2023, 32(9):5-9. (In Chinese), articleTitle=Research progress on the mechanism of resveratrol in the treatment of male infertility caused by sperm mitochondrial damage, refAbstract=null)], funds=[Fund(id=1324078154498835167, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, awardId=2022D01B149, language=CN, fundingSource=新疆维吾尔治区自然科学青年科学基金(2022D01B149), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1324078145426555514, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, xref=null, ext=[AuthorCompanyExt(id=1324078145443332731, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, companyId=1324078145426555514, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Xinjiang Second Medical College, Karamay, Xinjiang 834000, China), AuthorCompanyExt(id=1324078145455915644, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, companyId=1324078145426555514, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=新疆第二医学院，新疆 克拉玛依 834000)])], figs=[ArticleFig(id=1324078151353107151, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Figure 1, caption=TEM image of Nano-TiO2 (×15W), figureFileSmall=2r+fWYbwP73lqb+o5J++WA==, figureFileBig=nh0OYJITcnEee3GKDfrHhA==, tableContent=null), ArticleFig(id=1324078151432798928, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=图1, caption=Nano-TiO2颗粒的透射电镜图(×15W), figureFileSmall=2r+fWYbwP73lqb+o5J++WA==, figureFileBig=nh0OYJITcnEee3GKDfrHhA==, tableContent=null), ArticleFig(id=1324078151621542609, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Figure 2, caption=HE staining results of mouse testicular tissue (×400), figureFileSmall=WCFY5Bpjur4WvBdoEg2I8A==, figureFileBig=C1x9T2rVpqLYoJIy7DYMIA==, tableContent=null), ArticleFig(id=1324078151688651474, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=图2, caption=小鼠睾丸组织HE染色结果 (×400)

注：黑色箭头表示生精小管结构紊乱，各级生精细胞减少；黑色圆圈表示生精小管空泡化；黑色三角表示精子数减少；图A、B、C.D、E分别为A组、B组、C组、D组、E组。

, figureFileSmall=WCFY5Bpjur4WvBdoEg2I8A==, figureFileBig=C1x9T2rVpqLYoJIy7DYMIA==, tableContent=null), ArticleFig(id=1324078151772537555, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Figure 3, caption=Johnsen scores of testicular tissue in each group of mice（）, figureFileSmall=sknUuHgLLxZ6WzA4SBWnHQ==, figureFileBig=7fO7zfFQIqPR87okhUm7Dw==, tableContent=null), ArticleFig(id=1324078151835452116, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=图3, caption=各组小鼠睾丸组织Johnsen评分（）

注：与对照组相比，*P<0.05；与Nano-TiO2组相比，#P<0.05；图A、B、C.D、E分别为A组、B组、C组、D组、E组。

, figureFileSmall=sknUuHgLLxZ6WzA4SBWnHQ==, figureFileBig=7fO7zfFQIqPR87okhUm7Dw==, tableContent=null), ArticleFig(id=1324078151915143893, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Table 1, caption=

Body weight and organ coefficient of mice in each group ［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组体重(g)左侧睾丸系数(mg/g)右侧睾丸系数(mg/g)左侧附睾系数(mg/g)右侧附睾系数(mg/g)
A组31.11±2.574.04±0.264.09±0.371.24±0.441.23±0.50
B组31.62±3.113.81±0.473.84±0.491.09±0.461.10±0.52
C组30.82±2.294.16±0.434.20±0.361.16±0.431.30±0.51
D组29.79±2.434.03±0.394.14±0.421.19±0.491.22±0.51
E组28.60±2.60#4.39±0.25#4.62±0.41#1.30±0.461.33±0.46
), ArticleFig(id=1324078151994835670, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=表1, caption=

各组小鼠体重和脏器系数［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组体重(g)左侧睾丸系数(mg/g)右侧睾丸系数(mg/g)左侧附睾系数(mg/g)右侧附睾系数(mg/g)
A组31.11±2.574.04±0.264.09±0.371.24±0.441.23±0.50
B组31.62±3.113.81±0.473.84±0.491.09±0.461.10±0.52
C组30.82±2.294.16±0.434.20±0.361.16±0.431.30±0.51
D组29.79±2.434.03±0.394.14±0.421.19±0.491.22±0.51
E组28.60±2.60#4.39±0.25#4.62±0.41#1.30±0.461.33±0.46
), ArticleFig(id=1324078152129053399, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Table 2, caption=

Comparison of sperm and semen quality of mice in each group ［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组精子密度(106个/ml)精子进行性活力(%)精子活率(%)精子畸形率(%)
A组10.33±2.7644.50±17.2056.60±17.379.80±1.65
B组8.19±2.55*30.80±9.85*42.00±8.07*12.04±1.91*
C组8.89±2.7143.20±12.78#55.00±11.80#10.20±1.63#
D组7.90±1.8043.40±14.42#56.70±13.58#10.46±0.92#
E组8.44±1.5142.80±10.25#54.10±9.99#10.52±1.39#
), ArticleFig(id=1324078152229716696, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=表2, caption=

各组小鼠精子精液品质比较［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组精子密度(106个/ml)精子进行性活力(%)精子活率(%)精子畸形率(%)
A组10.33±2.7644.50±17.2056.60±17.379.80±1.65
B组8.19±2.55*30.80±9.85*42.00±8.07*12.04±1.91*
C组8.89±2.7143.20±12.78#55.00±11.80#10.20±1.63#
D组7.90±1.8043.40±14.42#56.70±13.58#10.46±0.92#
E组8.44±1.5142.80±10.25#54.10±9.99#10.52±1.39#
), ArticleFig(id=1324078152301019865, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Table 3, caption=

Comparison of sperm function enzymes in testicular sperm among the mouse groups ［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组ACP活力(金氏单位/g Prot)AKP活力(金氏单位/g Prot)LDH活性(U/g)
A组108.90±10.5355.13±4.832 129.67±261.91
B组60.22±6.11*25.72±0.97*1 331.62±145.08*
C组78.37±9.71#35.08±8.181 709.20±68.27#
D组75.46±9.3825.97±3.502 022.20±280.55#
E组68.60±11.0830.12±5.171 523.35±65.08
), ArticleFig(id=1324078152397488858, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=表3, caption=

各组小鼠精子睾丸功能酶比较［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组ACP活力(金氏单位/g Prot)AKP活力(金氏单位/g Prot)LDH活性(U/g)
A组108.90±10.5355.13±4.832 129.67±261.91
B组60.22±6.11*25.72±0.97*1 331.62±145.08*
C组78.37±9.71#35.08±8.181 709.20±68.27#
D组75.46±9.3825.97±3.502 022.20±280.55#
E组68.60±11.0830.12±5.171 523.35±65.08
), ArticleFig(id=1324078152477180635, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Table 4, caption=

Comparison of oxidation-antioxidation related indicators of testicular sperm in each group of mice ［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组丙二醛含量(nmol/mg)CAT活力(U/mg Prot)SOD活力(U/mg Prot)GSH含量(μmol/g)GPx活力(U/mg Prot)
A组3.18±0.614.27±0.2541.35±2.4332.59±1.7785.00±6.16
B组12.67±2.03*1.61±0.64*21.39±0.94*12.70±1.47*31.85±1.04*
C组4.59±0.42#2.55±0.4731.65±0.72#13.93±2.4745.89±5.01#
D组5.07±0.56#3.87±0.46#28.37±0.63#15.17±4.6846.78±3.39#
E组4.74±0.29#2.03±0.5925.41±1.92#15.34±2.0738.80±3.44#
), ArticleFig(id=1324078152552678108, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=表4, caption=

各组小鼠精子睾丸氧化-抗氧化相关指标比较［n=10，（）］

, figureFileSmall=null, figureFileBig=null, tableContent=
分组丙二醛含量(nmol/mg)CAT活力(U/mg Prot)SOD活力(U/mg Prot)GSH含量(μmol/g)GPx活力(U/mg Prot)
A组3.18±0.614.27±0.2541.35±2.4332.59±1.7785.00±6.16
B组12.67±2.03*1.61±0.64*21.39±0.94*12.70±1.47*31.85±1.04*
C组4.59±0.42#2.55±0.4731.65±0.72#13.93±2.4745.89±5.01#
D组5.07±0.56#3.87±0.46#28.37±0.63#15.17±4.6846.78±3.39#
E组4.74±0.29#2.03±0.5925.41±1.92#15.34±2.0738.80±3.44#
), ArticleFig(id=1324078154242982621, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=EN, label=Table 5, caption=

Correlation analysis of semen quality, testicular functional enzymes and oxidative damage-related indicators

, figureFileSmall=null, figureFileBig=null, tableContent=
精液品质及睾丸
功能酶		丙二醛CATSODGSHGPx
rP值rP值rP值rP值rP值
精子密度-0.1530.2900.1660.2480.2910.0410.3620.0100.2870.043
精子进行性活力-0.3690.0080.1950.1740.2420.0910.1720.2320.2510.079
精子活率-0.4200.0020.2500.0800.2630.0650.1600.2660.2390.095
精子畸形率0.4320.002-0.2490.081-0.4020.004-0.2010.161-0.3030.032
ACP-0.596<0.0010.710<0.0010.915<0.0010.836<0.0010.877<0.001
AKP-0.499<0.0010.549<0.0010.873<0.0010.833<0.0010.846<0.001
LDH-0.611<0.0010.878<0.0010.769<0.0010.551<0.0010.734<0.001
), ArticleFig(id=1324078154343645918, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324078139311260252, language=CN, label=表5, caption=

精液品质、睾丸功能酶与氧化损伤相关指标的相关性分析

, figureFileSmall=null, figureFileBig=null, tableContent=
精液品质及睾丸
功能酶		丙二醛CATSODGSHGPx
rP值rP值rP值rP值rP值
精子密度-0.1530.2900.1660.2480.2910.0410.3620.0100.2870.043
精子进行性活力-0.3690.0080.1950.1740.2420.0910.1720.2320.2510.079
精子活率-0.4200.0020.2500.0800.2630.0650.1600.2660.2390.095
精子畸形率0.4320.002-0.2490.081-0.4020.004-0.2010.161-0.3030.032
ACP-0.596<0.0010.710<0.0010.915<0.0010.836<0.0010.877<0.001
AKP-0.499<0.0010.549<0.0010.873<0.0010.833<0.0010.846<0.001
LDH-0.611<0.0010.878<0.0010.769<0.0010.551<0.0010.734<0.001
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白藜芦醇对纳米二氧化钛诱导的雄性小鼠生殖毒性的保护作用
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安红梅 , 张理弘 , 苗加乐 , 张婧卓 , 宋艾蔓 , 吾力克拜克·买合木提 , 曹先峰 , 温永昌 , 李琦 , 闫瑞英 , 任财进 , 包乾江 , 王佳煜 , 雷宇航
现代预防医学 | 实验技术及其应用 2026,53(3): 519-524
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现代预防医学 |实验技术及其应用 2026 , 53 (3) : 519 -524
白藜芦醇对纳米二氧化钛诱导的雄性小鼠生殖毒性的保护作用
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安红梅 , 张理弘, 苗加乐, 张婧卓, 宋艾蔓, 吾力克拜克·买合木提, 曹先峰, 温永昌, 李琦, 闫瑞英, 任财进, 包乾江, 王佳煜, 雷宇航
作者信息
  • 新疆第二医学院，新疆 克拉玛依 834000
通讯作者:
安红梅，E-mail:
作者简介:

安红梅(1994—)，女，硕士，讲师，研究方向：生殖毒理学与分子流行病学

Protective effect of resveratrol on reproductive toxicity induced by nano titanium dioxide in male mice
Hong-mei AN , Li-hong ZHANG, Jia-le MIAO, Jing-zhuo ZHANG, Ai-man SONG, WULIKEBAIKE-Maihemuti, Xian-feng CAO, Yong-chang WEN, Qi LI, Rui-ying YAN, Cai-jin REN, Qian-jiang BAO, Jia-yu WANG, Yu-hang LEI
Affiliations
  • Xinjiang Second Medical College, Karamay, Xinjiang 834000, China
出版时间: 2026-02-10 doi: 10.20043/j.cnki.MPM.202509470
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摘要
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目的

探究白藜芦醇是否对纳米二氧化钛(nano titanium dioxide，Nano-TiO2)诱导的雄性小鼠生殖毒性具有保护作用。

方法

50只健康雄性ICR小鼠随机分为对照组、Nano-TiO2组、Nano-TiO2和低中高剂量白藜芦醇混合组。连续灌胃28 d后，取附睾组织进行精液品质测定，并使用睾丸组织评估病理变化、睾丸组织特异性功能酶以及氧化损伤相关指标。

结果

Nano-TiO2灌胃处理后小鼠睾丸系数和附睾系数均下降，精子密度、活力显著降低(P<0.05)，精子畸形率显著升高(P<0.05)，睾丸生精小管中生精细胞数量减少，Johnsen评分明显下降(P<0.05)；酸性磷酸酶、碱性磷酸酶、乳酸脱氢酶活性以及谷胱甘肽过氧化物酶、超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽均显著下降(P<0.05)；丙二醛水平显著升高(P<0.05)。白藜芦醇干预后，与Nano-TiO2组相比，睾丸系数和附睾系数回升，精液品质和病理组织损伤明显好转(P<0.05)，酸性磷酸酶和乳酸脱氢酶活性均显著提高(P<0.05)，同时睾丸组织中丙二醛水平显著下降、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶活性明显上升(P<0.05)。经过相关性分析，抗氧化酶以及丙二醛与精液品质和睾丸功能酶之间存在显著关联性。

结论

白藜芦醇对Nano-TiO2诱导的雄性小鼠生殖毒性具有保护作用。

纳米二氧化钛  /  白藜芦醇  /  保护作用  /  雄性生殖毒性  /  精液品质
Objective

To investigate whether resveratrol has a protective effect against reproductive toxicity induced by nano titanium dioxide (Nano-TiO2) in male mice.

Methods

A total of 50 healthy male ICR mice were randomly divided into the control group, Nano-TiO2 group, and mixed groups with Nano-TiO2 plus low-, medium-, and high-dose resveratrol. After 28 days of continuous gavage, epididymal tissue was collected for semen quality measurement, and testicular tissue was used to evaluate pathological changes, testicular tissue-specific functional enzymes, and oxidative damage related indicators.

Results

After exposure to Nano-TiO2, the testicular and epididymal coefficients of mice decreased significantly (P<0.05), sperm density and vitality decreased significantly (P<0.05), sperm deformity rate increased significantly (P<0.05), the number of spermatogenic cells in the testicular seminiferous tubules decreased, and the Johnsen score decreased significantly (P<0.05).The activities of acid phosphatase, alkaline phosphatase, lactate dehydrogenase, glutathione peroxidase (GPx), superoxide dismutase, catalase, and reduced glutathione all decreased significantly (P<0.05), and the level of malondialdehyde increased significantly (P<0.05). After intervention with resveratrol, compared with the Nano-TiO2 exposed group, the testicular and epididymal coefficients increased, semen quality and pathological tissue damage improved significantly (P<0.05), acid phosphatase and lactate dehydrogenase activities were significantly increased (P<0.05), and malondialdehyde levels in testicular tissue decreased significantly, while superoxide dismutase, glutathione peroxidase, and catalase activities increased significantly (P<0.05). After correlation analysis, it was found that there was a significant correlation between antioxidant enzymes and malondialdehyde and the indicators of semen quality and testicular function enzymes.

Conclusion

Resveratrol has a protective effect against reproductive toxicity induced by Nano-TiO2 in male mice.

Nano titanium dioxide  /  Resveratrol  /  Protective effect  /  Male reproductive toxicity  /  Semen quality
安红梅, 张理弘, 苗加乐, 张婧卓, 宋艾蔓, 吾力克拜克·买合木提, 曹先峰, 温永昌, 李琦, 闫瑞英, 任财进, 包乾江, 王佳煜, 雷宇航. 白藜芦醇对纳米二氧化钛诱导的雄性小鼠生殖毒性的保护作用. 现代预防医学, 2026 , 53 (3) : 519 -524 . DOI: 10.20043/j.cnki.MPM.202509470
Hong-mei AN, Li-hong ZHANG, Jia-le MIAO, Jing-zhuo ZHANG, Ai-man SONG, WULIKEBAIKE-Maihemuti, Xian-feng CAO, Yong-chang WEN, Qi LI, Rui-ying YAN, Cai-jin REN, Qian-jiang BAO, Jia-yu WANG, Yu-hang LEI. Protective effect of resveratrol on reproductive toxicity induced by nano titanium dioxide in male mice[J]. Modern Preventive Medicine, 2026 , 53 (3) : 519 -524 . DOI: 10.20043/j.cnki.MPM.202509470
正文
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纳米二氧化钛(nano titanium dioxide，Nano-TiO2)是指在三维空间中至少有一维处于100nm以下的二氧化钛材料[1]。因为Nano-TiO2独特的小尺寸效应，能够通过多种途径进入人体并沉积于各脏器中，从而造成肺、肝、脑、睾丸等组织损伤[2]。已有研究表明，雄性小鼠暴露于Nano-TiO2后，睾丸组织生精小管空泡化，生精层厚度减小，精子密度和精子活动力显著降低，精子畸形率显著上升，最终导致睾丸组织损伤[3-4]。
白藜芦醇是一种从植物中提取的天然黄酮类多酚物质，已有的研究发现白藜芦醇能够有效清除细胞内活性氧，抗氧化作用明显强于维生素C和维生素E[5-6]。Hamdy等人[7-9]的研究发现，经过白藜芦醇预处理，顺铂、纳米氧化铁、双酚A等物质诱导的精子参数降低、精子异常的百分比升高以及生精小管直径和长度显著减少等睾丸组织损伤情况得到了有效改善。
为探讨白藜芦醇是否对Nano-TiO2诱导雄性小鼠生殖毒性具有保护作用。本研究拟通过建立Nano-TiO2诱导的睾丸损伤小鼠模型，观察白藜芦醇对小鼠睾丸组织结构和功能以及附睾精液品质的影响，为Nano-TiO2造成的雄性生殖毒性作用的预防和治疗提供参考。
1　材料与方法
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1.1　实验动物及分组
本研究小鼠饲养于新疆第二医学院实验动物中心，环境温度控制在(22±2)℃，相对湿度约50%，实验动物生产合格证号为：SCXK(新)2023-0001)。动物实验研究得到新疆第二医学院医学伦理审查委员会批准，批件号为IACUC-XSMC-KT-20250313-019。50只雄性ICR小鼠采用随机分组的方法将小鼠分为对照组(蒸馏水，A组)、Nano-TiO2组(50 mg/kg Nano-TiO2，B组)、低剂量白藜芦醇组(50 mg/kg Nano-TiO2+25 mg/kg白藜芦醇，C组)、中剂量白藜芦醇组(50 mg/kg Nano-TiO2+50 mg/kg白藜芦醇，D组)、高剂量白藜芦醇组(50 mg/kg Nano-TiO2+100 mg/kg白藜芦醇，E组)，每组10只。持续灌胃28 d，实验结束次日小鼠麻醉后颈椎脱臼处死并摘取睾丸和附睾组织，称重后计算睾丸系数和附睾系数。
1.2　实验材料与仪器
锐钛矿型Nano-TiO2购自上海阿拉丁生化技术有限公司；白藜芦醇购自北京索来宝有限公司；氯化钠购自上海晶纯试剂有限公司；苏木精伊红染液购自北京索来宝有限公司；微量移液器购自Eppendorf公司；光学显微镜购自宁波舜宇仪器有限公司。
1.3　精子悬液制备
取左侧附睾，使用生理盐水冲洗干净，放入盛有1 ml 37 ℃生理盐水的Ep管中，用眼科剪快速剪碎，吹打混匀，制成精子悬液，将悬液置于37 ℃水浴箱中孵育10 min。
1.4　精液品质的测定
精子密度的测定：取0.01 ml精子悬液滴加于血球细胞计数板的一侧，在显微镜下分别计数5个方格的精子数量(包括四角的四个方格和正中的一个方格)后确定每毫升精液中的精子数量。精子活率及精子进行性活力的测定：取0.01 ml精子悬液滴于血球细胞计数板中，在显微镜下记录运动精子数量和前向运动精子数量，分别除以精子总数即可。精子畸形率：取0.01 ml精子悬液滴加于载玻片中，选择500个精子中计数畸形的精子总数，计算畸形率。
1.5　睾丸组织病理切片的制作与观察
取睾丸组织于多聚甲醛液体中固定，将其包埋在石蜡块中，切成5 μm厚并置于单独的载玻片上，并用苏木精和伊红(hematoxylin-eosin, HE)染色，随后在×400倍光学显微镜下观察，观察睾丸组织病理学改变。为量化睾丸组织的病理表现，采用Johnsen病理评分对生精小管的生精功能进行评价。评分1～10分，完全丧失活性的小管评分为1分，具有最大活性的生精小管评分为10分。
1.6　睾丸组织特异性酶检测
采用市售酶联免疫吸附测定试剂盒(中国南京建成生物工程研究所)，按照制造商的说明，检测了睾丸组织中酸性磷酸酶(acid phosphatase,ACP)、碱性磷酸酶(alkaline phosphatase,AKP)、乳酸脱氢酶(lactate dehydrogenase,LDH)水平。
1.7　睾丸组织氧化损伤相关指标检测
采用市售酶联免疫吸附测定试剂盒(中国南京建成生物工程研究所)，按照制造商的说明，检测了睾丸组织中丙二醛、谷胱甘肽过氧化物酶(glutathione peroxidase，GPx)、超氧化物歧化酶 (superoxide dismutase，SOD)、过氧化氢酶(catalase，CAT)和还原型谷胱甘肽(reduced glutathione,GSH)水平。
1.8　统计学方法
使用SPSS 26.0软件进行数据整理与分析，所有图形采用Graphpad Prism软件绘制。多组间的比较采用单因素方差分析(one-way ANOVA)，应用LSD法进行多组间的多重比较。采用Pearson相关进行相关性分析。所有结果采用（均数±标准差）对数据描述。检验水准α=0.05。
2　结果
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2.1　Nano-TiO2的表征
透射电镜结果如图1所示，Nano-TiO2颗粒接近球形，晶体分布较为均匀；利用Image-J软件统计透射电镜图中的Nano-TiO2粒径，其大小约(18.92±2.43) nm。
2.2　小鼠体重、睾丸和附睾系数比较
与对照组相比，Nano-TiO2组的左右两侧睾丸脏器系数和左右两侧附睾脏器系数均下降，但无统计学差异(P>0.05)。与Nano-TiO2组相比，各个剂量的白藜芦醇均能够使左右两侧睾丸系数和附睾系数升高，其中100 mg/kg白藜芦醇则能够明显提高小鼠左右两侧睾丸脏器系数(P<0.05)。见表1。
2.3　附睾精液质量评定
小鼠附睾精子密度、精子活动率以及精子畸形率如表2所示。与对照组相比，连续28 d给予Nano-TiO2后，小鼠的精子密度、进行性精子活力、精子活率均显著下降(P<0.05)，精子畸形率明显增加(P<0.05)。与Nano-TiO2组相比，白藜芦醇使精子密度、进行性精子活力、精子活率均提高，精子畸形率均下降。尤其所有剂量的白藜芦醇均能够显著提升精子进行性活力和精子活率(P<0.05)，同时显著降低精子畸形率(P<0.05)。
2.4　睾丸组织病理学变化
睾丸组织病理学如图2所示。对照组小鼠的生精小管圆润饱满，管径较大，各级生精细胞有序排列，支持细胞散在分布于各级生精细胞间，睾丸间质细胞数量较多。与对照组相比，暴露于Nano-TiO2的小鼠睾丸组织中生精小管管径正常但部分边界模糊，各级生精细胞之间有明显的空泡化，部分管腔内生精细胞固缩，数量减少，排列紊乱，胞质致密，染色深，睾丸支持细胞和成型的精子数量较少。与Nano-TiO2组相比，各个剂量白藜芦醇和Nano-TiO2混合组的睾丸组织生精小管管径大部分正常，管腔较饱满，边界清晰，各级生精细胞之间有少量的空泡化，少部分管腔也发现生精细胞排列紊乱。
睾丸组织Johnsen病理评分结果如图3所示。与对照组相比，Nano-TiO2组Johnsen评分显著下降(P<0.05)，提示睾丸组织生精功能已发生中重度损伤。与Nano-TiO2组相比，25 mg/kg白藜芦醇和Nano-TiO2混合组评分显著升高(P<0.05)，白藜芦醇可修复Nano-TiO2导致的生精功能损伤。
2.5　睾丸功能相关酶检测
如表3所示，与对照组相比，Nano-TiO2组的ACP、AKP和LDH活性均显著下降。给予白藜芦醇后，25 mg/kg白藜芦醇能够使ACP活性显著回升(P<0.05)，25 mg/kg和50 mg/kg白藜芦醇均能够显著提高LDH活性(P<0.05)。
2.6　睾丸氧化-抗氧化相关指标的检测
为研究白藜芦醇对Nano-TiO2诱导的睾丸组织氧化损伤的缓解作用，氧化-抗氧化相关指标如表4所示。与对照组相比，暴露于Nano-TiO2后小鼠睾丸组织中的丙二醛水平显著升高，CAT、SOD、GSH、GPx活力均显著下降(P<0.05)。与Nano-TiO2组相比，所有剂量的白藜芦醇均能够使丙二醛显著下降、SOD和GPx活力显著提升(P<0.05)；此外，50 mg/kg白藜芦醇能够使CAT活性上升(P<0.05)。
2.7　精液品质、睾丸功能酶与氧化损伤相关指标的相关性分析
为进一步探究氧化损伤在白藜芦醇对Nano-TiO2诱导生殖毒性中的作用，对精液品质、睾丸功能酶与氧化损伤相关指标进行相关性分析。结果见表5，丙二醛与精子进行性活力、精子活率、ACP、AKP、LDH显著负相关，与精子畸形率显著正相关(P<0.05)。SOD、GSH、GPx与精子密度之间正相关，CAT、SOD、GSH、GPx与ACP、AKP、LDH均为正相关，SOD、GPx与精子畸形率显著负相关(P<0.05)。
3　讨论
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体重能够较全面反映小鼠的营养状态、生理情况和健康状况，而睾丸系数则是判断化学物对睾丸损伤的综合指标之一[10]。正常情况下小鼠的睾丸系数相对恒定，如果小鼠受到外源物质的严重影响，体重或睾丸重量可能会发生改变，最终导致了脏器系数的改变[11]。在本实验条件下，与对照组相比，Nano-TiO2组小鼠睾丸系数和附睾系数均降低，经过白藜芦醇干预后升高，尤其是100 mg/kg白藜芦醇能够显著提高左右两侧睾丸系数。Pasquariello等人[12]的研究也证实了白藜芦醇对于睾丸组织脏器系数的提升作用。
已有的研究表明，Nano-TiO2能够穿过血睾屏障从而不断在睾丸组织持续累积，从而导致了睾丸生精小管中各级各类生精细胞数量减少以及生精细胞间出现空泡化，Johnsen病理评分下降也提示了生精小管的生精功能发生障碍，因此附睾中的精子密度降低，ACP活性的显著下降也佐证了这一点[13-14]。同时，由于支持细胞和间质细胞受损，生精小管管径变窄以及管腔边界模糊，LDH和AKP水平下降，睾丸组织细胞能量代谢下降的同时维持精子发生成熟所需营养物质的转运也出现障碍，导致精子进行性活力、精子活率下降，精子畸形率升高[15-16]。综合作用下，暴露于Nano-TiO2后的小鼠睾丸的结构和功能以及附睾功能均受到损伤[17]。
与Nano-TiO2组相比，给予白藜芦醇后，混合组小鼠附睾精液品质以及睾丸组织病理表现和下降的功能酶活性均发生好转。已有的研究发现，白藜芦醇干预后，可以有效缓解被糖尿病和虎杖苷等物质引起的精子数量、活力和存活率的下降，减少了异常精子的数量[18]；同时睾丸组织的生精小管内细胞排列紊乱以及各级各类生精细胞减少的病理损伤被有效改善，作为健康精子发生指标的Johnsen评分回升，小鼠睾丸中ACP、LDH、琥珀酸脱氢酶等酶活性提升[19-21]。
另有研究显示，Nano-TiO2可导致睾丸组织内的活性氧生成过多，GPx、SOD、CAT和GSH等抗氧化酶和抗氧化物的活性降低，进而导致细胞发生脂质过氧化，产生过多的丙二醛，睾丸组织发生氧化损伤[22-23]。而白藜芦醇作为主要抗氧化物，通过提高睾丸和附睾组织中的主要抗氧化酶的活性、降低脂质过氧化标志物丙二醛水平、改善精子DNA损伤等途径从而缓解了味精、异氟醚等外源性物质诱导的雄性生殖器官损伤[24-25]。
值得注意的是，刘贵珊等人[26]采用与本研究相同剂量的白藜芦醇后发现，25、50和100 mg/kg白藜芦醇能够显著改善D-半乳糖致衰老小鼠的脑组织氧化损伤，SOD和总抗氧化能力活性显著升高，丙二醛含量降低，且具有剂量依赖性。在减轻玉米赤霉烯酮中毒小鼠肝脏损伤的研究中，相较于50和200 mg/kg白藜芦醇，100 mg/kg白藜芦醇的抗氧化效果最佳[27]。此外，还有研究表明，低浓度白藜芦醇可提高精子线粒体呼吸效率，而浓度增高时线粒体呼吸效率会显著降低，由此可能会影响到睾丸组织的氧化水平[28-29]。因此，在后期研究中需要关注白藜芦醇可能出现的“剂量依赖性双向效应”，白藜芦醇对雄性生殖毒性保护作用的外推需要谨慎考虑。
综上所述，雄性小鼠暴露于Nano-TiO2后，小鼠附睾精液品质降低，睾丸组织病理损伤增加、睾丸功能酶活性受到抑制，同时氧化产物增加、抗氧化酶水平降低，而白藜芦醇对Nano-TiO2诱导的睾丸及附睾损伤具有一定改善作用，可能是通过减轻睾丸组织氧化损伤实现。
本研究采用的部分指标如精子畸形率仅能够反映已出现明显形态改变的畸形精子比例，对于部分“形态正常精子但存在功能缺陷”的精子无法有效识别，后续实验中可通过“彗星实验”进一步验证精子的DNA损伤情况。此外本研究采取亚急性染毒实验，各组睾丸生精小管病理表现差异性不明显且未覆盖完整精子生成周期，未来可进行亚慢性或慢性实验观察到明显病理损伤。本研究未检测睾丸中Nano-TiO2蓄积量以及Nrf2/ARE通路，使得白藜芦醇拮抗Nano-TiO2诱导的雄性小鼠生殖毒性的机制以及完善性存在缺漏，后续研究可对其进一步完善。
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2026年第53卷第3期
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doi: 10.20043/j.cnki.MPM.202509470
  • 接收时间：2025-09-27
  • 首发时间：2026-11-02
  • 出版时间：2026-02-10
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新疆维吾尔治区自然科学青年科学基金(2022D01B149)
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    新疆第二医学院，新疆 克拉玛依 834000

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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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