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Article(id=1322926511635968609, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322926217711726961, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.08.039, 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=1793339859159, onlineDateStr=2026-10-30, pubDate=1754755200000, pubDateStr=2025-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339859159, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339859159, creator=13701087609, updateTime=1793339859159, 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=202, endPage=206, ext={EN=ArticleExt(id=1322926511837295202, articleId=1322926511635968609, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Bidirectional Regulation of Baishao（Radix Paeoniae Alba）Improving Intestinal Function in Rats with Irritable Bowel Syndrome, columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the effects of Baishao（Radix Paeoniae Alba）on rats with irritable bowel syndrome with diarrhea（IBS-D）and irritable bowel syndrome with constipation（IBS-C）.

Methods

Sixty-six SD male rats aged 4 weeks were randomly divided into normal control group，IBS-D model group，IBS-D drug group［high，medium and low doses of Baishao（Radix Paeoniae Alba）and pivilium bromide］，IBS-Cmodel group and IBS-C drug group［high，medium and low doses of Baishao（Radix Paeoniae Alba）and moxapride］.Acetic acid stimulation combined with binding stress was used for IBSD modeling，and ice water gavage combined with binding stress was used for IBS-C modeling.The high，medium and low dose groups were administrated with Baishao（Radix Paeoniae Alba）（7.2，3.6，1.8 g/kg body mass，respectively），piverium bromide aqueous solution（13.5 mg/kg）and moxabi aqueous solution（1.35 mg/kg）for 2 weeks，respectively.The weight was performed，the stool was collected，the abdominal withdrawal reflex（AWR）score was performed.The expressions of vasoactive intestinal peptide（VIP）and nuclear transcription factorκB（NF-κB）in ileocecal colon were detected by immunohistochemistry and ELISA.The expression of protease activating receptor 2（PAR2）in intestinal tissues was detected by Western blot.

Results

（1）IBS-D：Baishao（Radix Paeoniae Alba）at high，medium and low doses and piveronium bromide could improve visceral hypersensitivity in model rats（P<0.05，P<0.01，P<0.01，P<0.01，respectively）.Baishao（Radix Paeoniae Alba）at middle and low doses and piveronium bromide could reduce the fecal water content of model rats（P<0.01），but Baishao（Radix Paeoniae Alba）at high dose had no significant effect on reducing fecal water content of model rats（P>0.05）.The weight gain of model group was lower than that of the normal control group（P<0.01），and Baishao（Radix Paeoniae Alba）at high dose could reduce the weight gain of the model group（P<0.05）.Baishao（Radix Paeoniae Alba）at high dose could decrease the expression of NF-κB in model rats（P<0.01）.Baishao（Radix Paeoniae Alba）at high and medium doses could decrease the expression of PAR2 in model mice（P<0.01，P<0.05）.（2）IBS-C：Baishao（Radix Paeoniae Alba）at medium and low doses could improve visceral hypersensitivity of model rats（all P<0.05）.Baishao（Radix Paeoniae Alba）at high dose could increase fecal water content of model rats（P<0.01）.The weight gain of the model group was lower than that of the normal control group（P<0.05），and the drug group had no effect on the body weight of the model rats（all P>0.05）.Baishao（Radix Paeoniae Alba）at high dose and mosapride could decrease VIP expression in model rats（P<0.05，P<0.01）.Baishao（Radix Paeoniae Alba）at low dose could decrease PAR2 expression in IBS-Cmodel rats（P<0.05）.

Conclusion

Baishao（Radix Paeoniae Alba）can improve the visceral hypersensitivity of the rats with IBS-D and IBS-C at the same time，which may be related to the decrease of PAR2 expression.Medium and low doses of Baishao（Radix Paeoniae Alba）can alleviate diarrhea of the rats with IBS-D，while high doses of Baishao（Radix Paeoniae Alba）can promote defecation of the rats with IBS-C，which may be related to the difference of multi-target effects of Baishao（Radix Paeoniae Alba）on different models.

, authors=Liyuan TAO, Fang CHEN, Linlin SHI, authorsList=Liyuan TAO, Fang CHEN, Linlin SHI, authorCompany=null, correspAuthors=Linlin SHI, 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=1322926514878165618, articleId=1322926511635968609, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=白芍通过双向调节作用改善肠易激综合征大鼠肠道功能, columnId=1256183369033965799, journalTitle=中华中医药学刊, columnName=省级项目平台, runingTitle=null, highlight=null, articleAbstract=
目的

探讨白芍对腹泻型肠易激综合征（irritable bowel syndrome with diarrhea，IBS-D）和便秘型肠易激综合征（irritable bowel syndrome with constipation，IBS-C）大鼠的作用。

方法

4周龄SD雄性大鼠66只，随机均分为正常对照组、IBS-D模型组、IBS-D药物组（白芍高、中、低剂量及匹维溴铵）、IBS-C模型组、IBS-C药物组（白芍高、中、低剂量及莫沙必利）。采用乙酸刺激联合束缚应激进行IBS-D造模，冰水灌胃联合束缚应激进行IBS-C造模。药物组分别以白芍（高、中、低剂量组分别按7.2、3.6、1.8 g/kg体质量用药）和匹维溴铵水溶液（13.5 mg/kg）、莫沙必水溶液（1.35 mg/kg）灌胃2周。每周称重，实验结束后收集粪便，进行腹部撤离反射（abdominal withdrawal reflex，AWR）评分，免疫组化法检测大鼠回盲部结肠组织核转录因子κB（nuclear transcription factorκB，NF-κB）和血管活性肠肽（vasoactive intestinal peptide，VIP）的表达，Western blot检测肠组织中蛋白酶激活受体2（protease activating receptor 2，PAR2）的表达。

结果

（1）IBS-D各组比较：白芍高、中、低剂量及匹维溴铵均能改善模型大鼠内脏高敏感（分别为P<0.05，P<0.01，P<0.01，P<0.01）；白芍中、低剂量及匹维溴铵均能降低模型大鼠的粪便含水量（均P<0.01），白芍高剂量对于降低粪便含水量无明显作用（P>0.05）；模型组体质量增加量较正常对照组低（P<0.01），白芍高剂量组较模型组更低（P<0.05）；白芍高剂量能降低模型大鼠NF-κB表达（P<0.01）；白芍高、中剂量能降低模型鼠PAR2表达（P<0.01，P<0.05）。（2）IBS-C各组比较：白芍中、低剂量能改善模型大鼠内脏高敏感（均P<0.05）；白芍高剂量能提高模型大鼠的粪便含水量（P<0.01）；模型组体质量增加量较正常对照组低（P<0.05），药物组对模型大鼠体质量无影响（均P>0.05）；白芍高剂量和莫沙必利能降低模型大鼠VIP表达（P<0.05，P<0.01）；白芍低剂量能降低IBS-C模型大鼠PAR2表达（P<0.05）。

结论

白芍能同时改善IBS-D和IBS-C大鼠的内脏高敏感，可能和其能降低PAR2表达有关，其作用有剂量差异性；白芍中、低剂量能缓解IBS-D大鼠腹泻，白芍高剂量能促进IBS-C大鼠排便，这可能和白芍多靶点作用在不同模型上的作用差异有关。

, authors=陶丽媛, 陈芳, 施琳琳, authorsList=陶丽媛, 陈芳, 施琳琳, authorCompany=null, correspAuthors=施琳琳, authorNote=

陶丽媛（1988-），女，浙江平湖人，主治医师，硕士，研究方向：功能性胃肠病诊治。

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施琳琳（1980-），女，浙江杭州人，主任医师，硕士，研究方向：功能性胃肠病诊治。E-mail：。
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陶丽媛（1988-），女，浙江平湖人，主治医师，硕士，研究方向：功能性胃肠病诊治。

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陶丽媛（1988-），女，浙江平湖人，主治医师，硕士，研究方向：功能性胃肠病诊治。

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注：左至右依次为：正常对照组、IBS-D模型组、IBS-D+白芍高剂量组、IBS-D+白芍中剂量组、IBS-D+白芍低剂量组、IBS-D+匹维溴铵组、IBS-C模型组、IBS-C+白芍高剂量组、IBS-C+白芍中剂量组、IBS-C+白芍低剂量组、IBS-C+莫沙必利组，每组2份标本。

, figureFileSmall=NK2U4eVCLpsF1pKxsxbXVQ==, figureFileBig=3j0/ls0s5chTVXDqf4uqpQ==, tableContent=null), ArticleFig(id=1322926517264724629, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
分值大鼠行为表现
0分大鼠情绪基本稳定，无行为学反应
1分大鼠情绪不稳定，扭动头部
2分大鼠腹背部肌肉轻微收缩，但腹部未抬离地面
3分大鼠腹背部肌肉较强收缩，腹部抬离地面
4分大鼠腹背部肌肉强烈收缩，背部呈弓形并把腹部、骨盆及会阴部抬离地面
), ArticleFig(id=1322926517340222102, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=CN, label=表1, caption=

腹部撤离反射评分标准

, figureFileSmall=null, figureFileBig=null, tableContent=
分值大鼠行为表现
0分大鼠情绪基本稳定，无行为学反应
1分大鼠情绪不稳定，扭动头部
2分大鼠腹背部肌肉轻微收缩，但腹部未抬离地面
3分大鼠腹背部肌肉较强收缩，腹部抬离地面
4分大鼠腹背部肌肉强烈收缩，背部呈弓形并把腹部、骨盆及会阴部抬离地面
), ArticleFig(id=1322926518976000663, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nAWR=3的球囊压力/（mmHg）粪便含水量/（%）造模前体质量/（g）体质量增加量/（g）
正常对照组672.00±5.6657.66±1.36164.67±11.48147.17±13.53
IBS-D模型组653.33±4.13**76.24±11.21*161.17±10.32122.83±12.02**
IBS-D+白芍高剂量组660.67±3.93#64.41±12.39162.00±3.29110.67±7.69#
IBS-D+白芍中剂量组662.00±3.35##38.02±16.52##164.00±13.27118.50±9.57
IBS-D+白芍低剂量组664.00±3.58##42.43±21.62##158.83±4.88113.33±10.31
IBS-D+匹维溴铵组667.33±3.93##53.64±11.02##164.50±8.89119.33±4.93
IBS-C模型组655.33±7.34**29.91±14.01**165.67±7.74131.17±10.30*
IBS-C+白芍高剂量组660.00±4.3852.64±7.38▲▲156.50±8.55129.50±8.50
IBS-C+白芍中剂量组664.67±6.41▲▲42.93±15.73156.00±9.80127.50±9.93
IBS-C+白芍低剂量组665.33±3.27▲▲42.72±9.65163.17±8.47136.50±9.46
IBS-C+莫沙必利组658.67±4.1334.46±8.09162.83±6.37130.67±14.43
F值7.7036.9840.8296.287
P值0.0000.0000.6030.000
), ArticleFig(id=1322926519064081048, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=CN, label=表2, caption=

各组大鼠的检测数据（）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nAWR=3的球囊压力/（mmHg）粪便含水量/（%）造模前体质量/（g）体质量增加量/（g）
正常对照组672.00±5.6657.66±1.36164.67±11.48147.17±13.53
IBS-D模型组653.33±4.13**76.24±11.21*161.17±10.32122.83±12.02**
IBS-D+白芍高剂量组660.67±3.93#64.41±12.39162.00±3.29110.67±7.69#
IBS-D+白芍中剂量组662.00±3.35##38.02±16.52##164.00±13.27118.50±9.57
IBS-D+白芍低剂量组664.00±3.58##42.43±21.62##158.83±4.88113.33±10.31
IBS-D+匹维溴铵组667.33±3.93##53.64±11.02##164.50±8.89119.33±4.93
IBS-C模型组655.33±7.34**29.91±14.01**165.67±7.74131.17±10.30*
IBS-C+白芍高剂量组660.00±4.3852.64±7.38▲▲156.50±8.55129.50±8.50
IBS-C+白芍中剂量组664.67±6.41▲▲42.93±15.73156.00±9.80127.50±9.93
IBS-C+白芍低剂量组665.33±3.27▲▲42.72±9.65163.17±8.47136.50±9.46
IBS-C+莫沙必利组658.67±4.1334.46±8.09162.83±6.37130.67±14.43
F值7.7036.9840.8296.287
P值0.0000.0000.6030.000
), ArticleFig(id=1322926519139578521, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nNF-κB VIP
正常对照组69 581.57±5 276.931 205.11±1 141.12
IBS-D模型组619 146.45±3 473.99**2 470.30±1 876.62
IBS-D+白芍高剂量组610 009.89±7 446.65##2 301.31±1 388.19
IBS-D+白芍中剂量组616 698.68±8 981.252 237.23±1 435.07
IBS-D+白芍低剂量组619 331.22±7 445.551 442.64±1 257.16
IBS-D+匹维溴铵组614 006.72±3 717.441 398.45±948.19
IBS-C模型组612 142.72±5 621.452 656.00±2 781.32*
IBS-C+白芍高剂量组616 319.28±4 574.88980.46±976.11▲
IBS-C+白芍中剂量组616 854.71±3 428.442 420.17±2 114.95
IBS-C+白芍低剂量组614 466.61±7 309.452 035.10±1 545.53
IBS-C+莫沙必利组618 324.97±3 384.96475.19±973.98▲▲
统计值χ2=32.684χ2=23.248
P值0.0000.010
), ArticleFig(id=1322926519198298778, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=CN, label=表3, caption=

各组大鼠回盲部肠组织NF-κ B和VIP的总光密度（）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别nNF-κB VIP
正常对照组69 581.57±5 276.931 205.11±1 141.12
IBS-D模型组619 146.45±3 473.99**2 470.30±1 876.62
IBS-D+白芍高剂量组610 009.89±7 446.65##2 301.31±1 388.19
IBS-D+白芍中剂量组616 698.68±8 981.252 237.23±1 435.07
IBS-D+白芍低剂量组619 331.22±7 445.551 442.64±1 257.16
IBS-D+匹维溴铵组614 006.72±3 717.441 398.45±948.19
IBS-C模型组612 142.72±5 621.452 656.00±2 781.32*
IBS-C+白芍高剂量组616 319.28±4 574.88980.46±976.11▲
IBS-C+白芍中剂量组616 854.71±3 428.442 420.17±2 114.95
IBS-C+白芍低剂量组614 466.61±7 309.452 035.10±1 545.53
IBS-C+莫沙必利组618 324.97±3 384.96475.19±973.98▲▲
统计值χ2=32.684χ2=23.248
P值0.0000.010
), ArticleFig(id=1322926519277990555, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322926511635968609, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别nPAR2蛋白表达量
正常对照组60.20±0.05
IBS-D模型组60.27±0.03*
IBS-D+白芍高剂量组60.19±0.03##
IBS-D+白芍中剂量组60.20±0.02#
IBS-D+白芍低剂量组60.23±0.06
IBS-D+匹维溴铵组60.23±0.09
IBS-C模型组60.18±0.07
IBS-C+白芍高剂量组60.20±0.02
IBS-C+白芍中剂量组60.14±0.02
IBS-C+白芍低剂量组60.11±0.01▲
IBS-C+莫沙必利组60.12±0.04
统计值F=5.413
P值0.000
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各组大鼠回盲部肠组织PAR2的检测数据（）

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组别nPAR2蛋白表达量
正常对照组60.20±0.05
IBS-D模型组60.27±0.03*
IBS-D+白芍高剂量组60.19±0.03##
IBS-D+白芍中剂量组60.20±0.02#
IBS-D+白芍低剂量组60.23±0.06
IBS-D+匹维溴铵组60.23±0.09
IBS-C模型组60.18±0.07
IBS-C+白芍高剂量组60.20±0.02
IBS-C+白芍中剂量组60.14±0.02
IBS-C+白芍低剂量组60.11±0.01▲
IBS-C+莫沙必利组60.12±0.04
统计值F=5.413
P值0.000
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白芍通过双向调节作用改善肠易激综合征大鼠肠道功能
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陶丽媛 , 陈芳 , 施琳琳
中华中医药学刊 | 省级项目平台 2025,43(8): 202-206
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中华中医药学刊 |省级项目平台 2025 , 43 (8) : 202 -206
白芍通过双向调节作用改善肠易激综合征大鼠肠道功能
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陶丽媛, 陈芳, 施琳琳
作者信息
  • 浙江省中西医结合医院，浙江 杭州 310003
通讯作者:
施琳琳（1980-），女，浙江杭州人，主任医师，硕士，研究方向：功能性胃肠病诊治。E-mail：。
作者简介:

陶丽媛（1988-），女，浙江平湖人，主治医师，硕士，研究方向：功能性胃肠病诊治。

Bidirectional Regulation of Baishao（Radix Paeoniae Alba）Improving Intestinal Function in Rats with Irritable Bowel Syndrome
Liyuan TAO, Fang CHEN, Linlin SHI
Affiliations
  • Integrated Traditional Chinese and Western Medicine Hospital of Zhejiang Province，Hangzhou 310003，Zhejiang，China
出版时间: 2025-08-10 doi: 10.13193/j.issn.1673-7717.2025.08.039
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摘要
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目的

探讨白芍对腹泻型肠易激综合征（irritable bowel syndrome with diarrhea，IBS-D）和便秘型肠易激综合征（irritable bowel syndrome with constipation，IBS-C）大鼠的作用。

方法

4周龄SD雄性大鼠66只，随机均分为正常对照组、IBS-D模型组、IBS-D药物组（白芍高、中、低剂量及匹维溴铵）、IBS-C模型组、IBS-C药物组（白芍高、中、低剂量及莫沙必利）。采用乙酸刺激联合束缚应激进行IBS-D造模，冰水灌胃联合束缚应激进行IBS-C造模。药物组分别以白芍（高、中、低剂量组分别按7.2、3.6、1.8 g/kg体质量用药）和匹维溴铵水溶液（13.5 mg/kg）、莫沙必水溶液（1.35 mg/kg）灌胃2周。每周称重，实验结束后收集粪便，进行腹部撤离反射（abdominal withdrawal reflex，AWR）评分，免疫组化法检测大鼠回盲部结肠组织核转录因子κB（nuclear transcription factorκB，NF-κB）和血管活性肠肽（vasoactive intestinal peptide，VIP）的表达，Western blot检测肠组织中蛋白酶激活受体2（protease activating receptor 2，PAR2）的表达。

结果

（1）IBS-D各组比较：白芍高、中、低剂量及匹维溴铵均能改善模型大鼠内脏高敏感（分别为P<0.05，P<0.01，P<0.01，P<0.01）；白芍中、低剂量及匹维溴铵均能降低模型大鼠的粪便含水量（均P<0.01），白芍高剂量对于降低粪便含水量无明显作用（P>0.05）；模型组体质量增加量较正常对照组低（P<0.01），白芍高剂量组较模型组更低（P<0.05）；白芍高剂量能降低模型大鼠NF-κB表达（P<0.01）；白芍高、中剂量能降低模型鼠PAR2表达（P<0.01，P<0.05）。（2）IBS-C各组比较：白芍中、低剂量能改善模型大鼠内脏高敏感（均P<0.05）；白芍高剂量能提高模型大鼠的粪便含水量（P<0.01）；模型组体质量增加量较正常对照组低（P<0.05），药物组对模型大鼠体质量无影响（均P>0.05）；白芍高剂量和莫沙必利能降低模型大鼠VIP表达（P<0.05，P<0.01）；白芍低剂量能降低IBS-C模型大鼠PAR2表达（P<0.05）。

结论

白芍能同时改善IBS-D和IBS-C大鼠的内脏高敏感，可能和其能降低PAR2表达有关，其作用有剂量差异性；白芍中、低剂量能缓解IBS-D大鼠腹泻，白芍高剂量能促进IBS-C大鼠排便，这可能和白芍多靶点作用在不同模型上的作用差异有关。

肠易激综合征  /  内脏高敏感  /  白芍  /  血管活性肠肽  /  蛋白酶激活受体2
Objective

To investigate the effects of Baishao（Radix Paeoniae Alba）on rats with irritable bowel syndrome with diarrhea（IBS-D）and irritable bowel syndrome with constipation（IBS-C）.

Methods

Sixty-six SD male rats aged 4 weeks were randomly divided into normal control group，IBS-D model group，IBS-D drug group［high，medium and low doses of Baishao（Radix Paeoniae Alba）and pivilium bromide］，IBS-Cmodel group and IBS-C drug group［high，medium and low doses of Baishao（Radix Paeoniae Alba）and moxapride］.Acetic acid stimulation combined with binding stress was used for IBSD modeling，and ice water gavage combined with binding stress was used for IBS-C modeling.The high，medium and low dose groups were administrated with Baishao（Radix Paeoniae Alba）（7.2，3.6，1.8 g/kg body mass，respectively），piverium bromide aqueous solution（13.5 mg/kg）and moxabi aqueous solution（1.35 mg/kg）for 2 weeks，respectively.The weight was performed，the stool was collected，the abdominal withdrawal reflex（AWR）score was performed.The expressions of vasoactive intestinal peptide（VIP）and nuclear transcription factorκB（NF-κB）in ileocecal colon were detected by immunohistochemistry and ELISA.The expression of protease activating receptor 2（PAR2）in intestinal tissues was detected by Western blot.

Results

（1）IBS-D：Baishao（Radix Paeoniae Alba）at high，medium and low doses and piveronium bromide could improve visceral hypersensitivity in model rats（P<0.05，P<0.01，P<0.01，P<0.01，respectively）.Baishao（Radix Paeoniae Alba）at middle and low doses and piveronium bromide could reduce the fecal water content of model rats（P<0.01），but Baishao（Radix Paeoniae Alba）at high dose had no significant effect on reducing fecal water content of model rats（P>0.05）.The weight gain of model group was lower than that of the normal control group（P<0.01），and Baishao（Radix Paeoniae Alba）at high dose could reduce the weight gain of the model group（P<0.05）.Baishao（Radix Paeoniae Alba）at high dose could decrease the expression of NF-κB in model rats（P<0.01）.Baishao（Radix Paeoniae Alba）at high and medium doses could decrease the expression of PAR2 in model mice（P<0.01，P<0.05）.（2）IBS-C：Baishao（Radix Paeoniae Alba）at medium and low doses could improve visceral hypersensitivity of model rats（all P<0.05）.Baishao（Radix Paeoniae Alba）at high dose could increase fecal water content of model rats（P<0.01）.The weight gain of the model group was lower than that of the normal control group（P<0.05），and the drug group had no effect on the body weight of the model rats（all P>0.05）.Baishao（Radix Paeoniae Alba）at high dose and mosapride could decrease VIP expression in model rats（P<0.05，P<0.01）.Baishao（Radix Paeoniae Alba）at low dose could decrease PAR2 expression in IBS-Cmodel rats（P<0.05）.

Conclusion

Baishao（Radix Paeoniae Alba）can improve the visceral hypersensitivity of the rats with IBS-D and IBS-C at the same time，which may be related to the decrease of PAR2 expression.Medium and low doses of Baishao（Radix Paeoniae Alba）can alleviate diarrhea of the rats with IBS-D，while high doses of Baishao（Radix Paeoniae Alba）can promote defecation of the rats with IBS-C，which may be related to the difference of multi-target effects of Baishao（Radix Paeoniae Alba）on different models.

irritable bowel syndrome  /  visceral hypersensitivity  /  Baishao（Radix Paeoniae Alba）  /  vasoactive intestinal peptide  /  protease activating receptor 2
陶丽媛, 陈芳, 施琳琳. 白芍通过双向调节作用改善肠易激综合征大鼠肠道功能. 中华中医药学刊, 2025 , 43 (8) : 202 -206 . DOI: 10.13193/j.issn.1673-7717.2025.08.039
Liyuan TAO, Fang CHEN, Linlin SHI. Bidirectional Regulation of Baishao（Radix Paeoniae Alba）Improving Intestinal Function in Rats with Irritable Bowel Syndrome[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (8) : 202 -206 . DOI: 10.13193/j.issn.1673-7717.2025.08.039
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肠易激综合征（irritable bowel syndrome，IBS）是一种表现为反复腹痛或腹部不适，伴排便习惯改变的功能性肠病，分为腹泻型肠易激综合征（irritable bowel syndrome with diarrhea，IBS-D）、便秘型肠易激综合征（irritable bowel syndrome with constipation，IBS-C）、混合型肠易激综合征（irritable bowel syndrome with mixed bowel habits，IBS-M）和未定型肠易激综合征（irritable bowel syndrome unclassified，IBS-U）[1]。我国普通人群中IBS的患病率为1.4%～11.5%[2]；国外研究显示，IBS患者占消化科门诊总量的25%～50%，青少年患病率高达30.2%[1，3-4]。虽然IBS发病率高，但是仍缺乏有效治疗手段，许多药物仅能改善症状，而不能治愈疾病。在过去的几十年中，一些创新药物（如西沙必利）由于其严重的不良反应而被撤回[5]。尽管进行了许多与IBS病理过程相关的研究，但安全且有效的药物，仍需要进一步研究获得。
依据中医理论[6]，IBS可归于“腹痛”“便秘”和“泄泻”等范畴。中医认为IBS病位在肠，主要涉及肝、脾（胃）、肾等脏腑，肝郁脾虚是重要病机。以肝郁脾虚为基本病机，行“理气疏肝，润肠通便”之法的理气通便合剂在IBS-C患者的治疗中疗效显著[7]；肝郁脾虚的代表方痛泻要方能下调炎症相关因子，有效缓解IBS-D患者内脏高敏感及腹泻症状[8]。白芍，是理气通便合剂和痛泻要方共有的一味中药，一项基于生物信息学/网络拓扑策略的综合研究发现白芍有望成为新的IBS的治疗药物[9]，但是具体机制尚不明确。
本文以白芍单药干预IBS大鼠模型，探讨其对IBS-D和IBS-C模型大鼠的作用及可能的机制。
1　材料与方法
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1.1　动物
4周龄SPF级雄性SD大鼠66只，购于上海市计划生育科学研究所实验动物经营部，实验动物生产许可证号：SCXK（沪）2018-0006；饲养于浙江中医药大学动物实验研究中心屏障环境，实验动物使用许可证号：SYXK（浙）2021-0012；所有的动物实验操作都经过浙江中医药大学伦理委员会的审批（批准编号：IACUC-20210823-03）。
1.2　药物
白芍由浙江省中西医结合医院中药房提供，浸泡、煎煮、过滤、浓缩至2 g/m L（按生药量计），保存于4℃冰箱中备用，用前加温至37℃。枸橼酸莫沙必利片5 mg/片，产品批号：26220207，鲁南贝特制药有限公司。匹维溴铵片50 mg/片，产品批号：714641，MYLANLABORATORIESSAS。
1.3　主要试剂与仪器
8F气囊导尿管（湛江市事达实业有限公司），antiNF-κB抗体（catno.ab32360；Abcam，英国），anti-VIP抗体（catno.ab272726；Abcam，英国），Anti-PAR2抗体（catno.ab180953；Abcam，英国），蛋白提取试剂盒（凯基生物lot：20220110），蛋白BCA定量试剂盒（凯基生物lot：20211020），Protein simple试剂盒（凯基生物lot：65204），生物样品均质机（法国BIRTIN，Precellys 24），冷冻高速离心机（美国Thermo，Fresco 17），生化培养箱（上海博讯实业有限公司医疗设备厂，SPC-150BZ），酶标仪（Thermo VARIOSKAN FLASH），WES全自动蛋白表达分析系统（Protein simple）。
1.4　动物分组、造模及干预方法
4周龄SD大鼠适应性喂养1周，以随机数字表法将66只SD大鼠随机分为正常对照组、IBS-D模型组、IBS-D药物组（白芍高、中、低剂量及匹维溴铵）、IBS-C模型组、IBS-C药物组（白芍高、中、低剂量及莫沙必利），每组各6只。采用乙酸刺激联合束缚应激[10]对IBS-D模型组和IBS-D药物组进行造模，冰水灌胃联合束缚应激[11]对IBS-C模型组和IBSC药物组进行造模。根据体表面积换算[12]计算药物干预剂量。白芍高、中、低剂量组分别按7.2、3.6、1.8 g/kg体质量（分别相当于成人每日服用80、40、20 g白芍煎剂），莫沙必利水溶液［1.35 mg/（kg·d）］，匹维溴铵水溶液［13.5 mg/（kg·d）］，IBS-C造模组和IBS-D造模组予常温蒸馏水灌胃2 mL，1次/d，灌胃14 d。
1.5　观察指标及方法
1.5.1　大鼠一般情况及内脏敏感性测定
大鼠禁食不禁水12 h，将8F气囊导尿管带气囊一端甘油润滑后经肛门缓慢轻柔地插入5 cm，医用胶布固定在尾巴上，30 min后大鼠适应环境呈安静状态，扩张球囊使球囊内压力逐渐升高，根据大鼠腹部撤离反射（abdominal withdrawal reflex，AWR）评分标准[11，13]评估肠道敏感性。见表1。
1.5.2　粪便含水量及体质量增加量计算
在造模前及实验进行中每周进行每只大鼠称重，记录，计算出每只大鼠的体质量增加量，进行汇总统计。观察粪便性状，以Bristol分型进行评价[14]。末次给药后，采用代谢笼收集大鼠4 h粪便，迅速称量湿重，然后烘干，称量干重。粪便含水量（%）＝（粪便湿重-粪便干重）/粪便湿重×100%。
1.5.3　免疫组化法检测回盲部结肠组织核转录因子κB（nuclear transcription factorκB，NF-κB）和血管活性肠肽（vasoactive intestinal peptide，VIP）的表达
药物干预治疗14 d后，禁食24 h，不限水，以CO2窒息法进行安乐死，迅速取出近回盲部结肠1.0 cm，固定、脱水、包埋、切片、烤片，二甲苯、梯度乙醇水化，滴加3%H2 O2，一抗、二抗（稀释浓度参照说明书），室温孵育，DAB显色，拍照；Image-Pro Plus软件分析。
1.5.4　Western blot检测回盲部结肠组织蛋白酶激活受体2（protease activating receptor 2，PAR2）的表达
获取的近回盲部结肠冻存于液氮中，取出标本，研磨，加含蛋白酶抑制剂的蛋白提取试剂，匀浆，提总蛋白。BCA法测定样品浓度。根据试剂盒内附的说明书要求进行操作，配制一抗，一抗用Antibody DiluentⅡ稀释后放在冰上待用，二抗PAR2（1∶2000），配制发光液，将配制好的试剂依次加入板内，上机进行检测。
1.6　统计学方法
应用SPSS17.0统计学软件。计量资料以表示，正态分布且方差齐的数据，两组间比较采用两独立样本t检验，多组间比较采用单因素方差分析、用LSD Tests检验；非正态分布的数据，两组间比较采用Mann Whitney U检验，多组间比较采用Kruskal-Wallis检验。P<0.05为差异有统计学意义。
2　实验结果
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2.1　一般情况
实验期间无大鼠死亡。正常对照组大鼠精神状态好，Bristol分型多呈3型；IBS-D模型组大鼠精神状态不佳，易激惹，粪质稀烂，Bristol分型多呈4～5型；IBS-C模型组大鼠精神状态不佳，易激惹，粪质干硬，Bristol分型多呈1～2型。
2.2　各组大鼠内脏敏感性比较
IBS-D：IBS-D模型组的内脏敏感性高于正常对照组（P<0.01），药物干预后，白芍高、中、低剂量及匹维溴铵均能改善IBS-D模型大鼠内脏高敏感（分别为P<0.05，P<0.01，P<0.01，P<0.01）。
IBS-C：IBS-C模型组的内脏敏感性高于正常对照组（P<0.01），药物干预后，白芍中、低剂量能改善IBS-C模型大鼠内脏高敏感（均P<0.05）。
提示，白芍能改善IBS模型大鼠的内脏高敏感，但是高剂量白芍对于IBS-C模型大鼠无作用。见表2。
2.3　各组大鼠粪便含水量比较
IBS-D：各组间粪便含水量差异有统计学意义（P<0.01），IBS-D模型组高于正常对照组（P<0.05），符合模型特点；药物干预后，与IBS-D模型组比较，白芍中、低剂量及匹维溴铵均能降低模型大鼠的粪便含水量（均P<0.01），白芍高剂量对于降低粪便含水量无明显作用（P>0.05）。
IBS-C：各组间粪便含水量差异有统计学意义（P<0.01），IBS-C模型组低于正常对照组（P<0.01），符合模型特点；药物干预后，与IBS-C模型组比较，白芍高剂量能提高模型大鼠的粪便含水量（P<0.01）。
提示，白芍高剂量有助于通便，中、低剂量有助于改善腹泻症状。见表2。
2.4　各组大鼠体质量增加量比较
IBS-D：造模前，各组大鼠的体质量差异无统计学意义（P>0.05）；造模及药物干预结束后，IBS-D模型组较正常对照组低（P<0.01），白芍高剂量组较IBS-D模型组更低（P<0.05），其余药物组对模型大鼠体质量无影响（均P>0.05）。
IBS-C：造模前，各组大鼠的体质量差异无统计学意义（P>0.05）；造模及药物干预结束后，IBS-C模型组较正常对照组低（P<0.05），药物组对模型大鼠体质量无影响（均P>0.05）。
提示，IBS的造模影响大鼠的体质量增加，白芍对于体质量的增加不产生正性影响，高剂量白芍会阻碍IBS-D模型鼠的体质量增长。见表2。
2.5　各组大鼠回盲部结肠组织NF-κB和VIP比较
IBS-D：①模型组较正常对照组NF-κB表达升高（P<0.01），与模型组比较，白芍高剂量能降低模型组NF-κB表达（P<0.01）；②模型组较正常对照组VIP表达升高，与模型组比较，白芍、匹维溴铵能降低模型大鼠的VIP表达，但是差异无统计学意义。
IBS-C：①模型组较正常对照组NF-κB表达升高，差异无统计学意义，药物组与模型组间差异无统计学意义；②模型组VIP表达较正常对照组升高（P<0.05），与模型组比较，白芍高剂量和莫沙必利能降低模型大鼠的VIP表达（P<0.05，P<0.01）。见插页LⅡ图1、插页LⅢ图2、表3。
2.6　各组大鼠回盲部结肠组织PAR2表达比较
IBS-D：模型组回盲部结肠组织中PAR2表达较正常对照组高（P<0.05），白芍高、中剂量能降低模型鼠PAR2表达（P<0.01，P<0.05）。
IBS-C：模型组较正常对照组差异无统计学意义，白芍中、低剂量均能降低IBS-C模型大鼠PAR2表达，低剂量组差异有统计学意义（P<0.05）。见图3、表4。
3　讨论
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白芍，味苦、酸，性微寒，归肝、脾经，具有柔肝疏肝、调和肝脾、缓急止痛及通利二便等作用。《名医别录》[15]记载其可以利膀胱大小肠，说明有通利大小便的作用。《本草求真》[16]记载其能土中泻木，可通过调肝和脾而达到缓解腹痛的作用。白芍广泛应用于IBS的临床实践中，陈思思[17]将316例IBS-D病案的713首处方进行分析，共涉及中药103味，发现白芍在IBS-D处方中的使用频次是最高的；罗茂权等[18]分析了233首治疗IBS-C的处方，共涉及中药189味，发现白芍在IBSC处方中的使用频次也是最高的，且白芍在不同证型IBS中均得到广泛使用。
依据现代研究结果[19-20]，IBS的发生可能与内脏高敏感、黏膜炎症、免疫激活、上皮细胞通透性改变、肠道菌群紊乱、遗传因素以及脑-肠轴作用等相关，其中内脏高敏感是基本的病理生理变化，目前的许多研究均以内脏高敏感性的变化来检验药物对于IBS的缓解作用。本实验中，以经典的AWR评估系统进行评估，提示白芍能同时改善IBS-D和IBS-C大鼠的内脏高敏感。
白芍具有抗炎及镇痛作用，可以通过抑制NF-κB信号通路有效降低过敏反应，抑制异常活化细胞亚群和恢复调节细胞亚群来平衡免疫细胞亚群，抑制促炎因子的释放以提高慢性炎症疼痛模型小鼠的痛阈值，能缓解感染后IBS模型鼠的腹痛腹泻症状[21-24]。本实验中，白芍能抑制IBS-D模型大鼠结肠NF-κB的高表达并起到镇痛作用，从而缓解模型鼠的内脏高敏感及腹泻症状。
PAR2与IBS内脏高敏感密切相关。PAR2是一种G蛋白偶联受体，在胃肠中广泛表达，参与胃肠运动、肠道内分泌、内脏疼痛等病理生理反应，一系列生物活性物质可激活PAR2进行伤害信号放大，导致IBS内脏高敏感[25]。本实验中，白芍能抑制IBS模型PAR2的表达，尤其是IBS-D模型PAR2高表达，相较于NF-κB，它的变化更加明显，笔者推测，白芍降低内脏高敏感可能与降低PAR2表达直接有关。
VIP广泛存在于胃肠道和中枢神经系统，能抑制胃肠蠕动，能促进肠道水和电解质的分泌，不管是在IBS-C还是IBS-D患者中，VIP的水平都是升高的[26-27]。VIP含量升高可增高肠道对外来刺激的敏感度，与患者的腹痛及排便性状改变等有关[28]。本实验中，白芍能降低IBS模型鼠肠组织中VIP含量，而IBS-C模型鼠的VIP含量较正常对照组升高更明显，同时，白芍高剂量组明显降低IBS-C模型VIP水平，这提示高剂量白芍对于便秘疗效更显著。这与我国很多中医案例符合，卢一颖等[29]重用生白芍辅助六磨汤治疗气机郁滞型便秘患者有良好效果。因此，笔者推测，高剂量白芍降低VIP表达，使胃肠道蠕动增强，从而通便作用占优，这也是白芍高剂量并没有降低IBS-D模型鼠粪便含水量，同时也阻碍其体质量增加的原因。
本实验中，白芍对于腹泻与便秘的双向调节作用，是既对立又统一的存在，是基于剂量的差异性作用，同时也与不同类型IBS模型本身的特性相关。IBS-C模型存在VIP表达异常，高剂量白芍对于VIP的作用有助于促进胃肠蠕动，减少大便在肠道中的水分吸收，从而提高IBS-C大鼠的粪便含水量，改善便秘。IBS-D模型存在炎症，白芍的抗炎作用使它能抑制IBS-D模型的肠道炎症及腹泻作用。而中、低剂量白芍的通便作用弱，但其能抗炎及降低PAR2表达，故能缓解不同类型IBS大鼠的腹痛症状。
本实验将白芍单药分别作用于IBS-C和IBS-D模型，探讨了其作用及机制，是基于一定的临床实践的引申，但落实到动物实验，仍存在一定的不足：IBS发病机制复杂，涉及多方面的因素，白芍的作用有基于量上的差别，且对于IBS的影响是多靶点作用的结果，涉及复杂的机制；同时，为了增加可操作性，本研究每组例数偏少，可能导致某些结果呈现假阴性，所以需要进一步更大样本的研究。
综上，白芍能同时改善IBS-D和IBS-C大鼠的内脏高敏感，可能和其能降低PAR2表达有关，其作用有剂量差异性；白芍中、低剂量能缓解IBS-D大鼠腹泻，白芍高剂量能促进IBS-C大鼠排便。未来需要更深入地研究探讨白芍的多靶点作用机制。
基金
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  • 浙江省中医药科技计划项目(2021ZB216; 2023ZF146)
  • 浙江省自然科学基金项目(LQN25H290006)
  • 杭州市医药卫生科技项目(A20230125)
文献
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doi: 10.13193/j.issn.1673-7717.2025.08.039
  • 首发时间：2026-10-30
  • 出版时间：2025-08-10
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浙江省中医药科技计划项目(2021ZB216; 2023ZF146)
浙江省自然科学基金项目(LQN25H290006)
杭州市医药卫生科技项目(A20230125)
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    浙江省中西医结合医院，浙江 杭州 310003

通讯作者:

施琳琳（1980-），女，浙江杭州人，主任医师，硕士，研究方向：功能性胃肠病诊治。E-mail：。
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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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