文献类型：期刊文献

中文题名：基于p38/MLCK信号通路探讨疏肝止泻方对肝郁脾虚型腹泻型肠易激综合征大鼠肠道通透性的影响

英文题名：Effects of Shugan Zhixie Formula on intestinal permeability of diarrheal irritable bowel syndrome rats with Liver Depression and Spleen Deficiency based on p38/MLCK signaling pathway

作者：赖学倩[1];刘俊宏[2];李亚静[2];王淼蕾[2];张金雪[3];王丹[3];苏李宁[3];王亮[1]

第一作者：赖学倩

机构：[1]甘肃省妇幼保健院(甘肃省中心医院),甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000;[3]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃省妇幼保健院(甘肃省中心医院),甘肃兰州730000

年份：2026

卷号：48

期号：4

起止页码：1156

中文期刊名：中成药

外文期刊名：Chinese Traditional Patent Medicine

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金(81660773);2022年青年岐黄学者基金项目(国中医药人教函[2022]256号);甘肃省科学技术厅重点研发计划项目(22YFTFA100);甘肃省卫生健康委员会项目(21JR7RA682);中共甘肃省委组织部省级重点人才项目(2022RCXM020);甘肃省中医药管理局重点项目(GZKZ-2021-6);甘肃省卫生行业科研计划项目(GSWSQN2022-01);兰州市科技计划项目(2021-1-98);甘肃中医药大学附属医院院内课题(gzfy-2021-14)。

语种：中文

中文关键词：疏肝止泻方;腹泻型肠易激综合征;肝郁脾虚证;肠道通透性;肠道炎症;p38/MLCK信号通路

外文关键词：Shugan Zhixie Formula;diarrhea irritable bowel syndrome;Liver Depression and Spleen Deficiency;intestinal permeability;intestinal inflammation;p38/MLCK signaling pathway

摘要：目的 探讨疏肝止泻方对肝郁脾虚型腹泻型肠易激综合征(IBS-D)大鼠肠道通透性的影响。方法 50只雄性Wistar大鼠随机分为空白组、模型组、匹维溴铵组(0.013 5 g/kg)及疏肝止泻方低、中、高剂量组(2.57、5.13、10.26 g/kg)。除空白组外,其余组均以饥饱失常+束缚夹尾应激+肠道灌注乙酸建立肝郁脾虚型IBS-D大鼠模型。给药干预后,HE染色观察结肠组织形态;ELISA法检测血浆D-LA水平及血清TNF-α、IL-1β、IL-6水平;Western blot、RT-qPCR法检测结肠组织GDNF、S100β、iNOS、ZO-1蛋白及mRNA表达;免疫组织化学法检测结肠组织p38、MLCK蛋白表达。结果 与空白组比较,模型组大鼠结肠黏膜中有少量炎性细胞浸润,体质量降低(P<0.01);血浆D-LA水平及血清TNF-α、IL-1β、IL-6水平升高(P<0.01);结肠组织p38、MLCK蛋白表达升高(P<0.01),GDNF、S100β、ZO-1蛋白和mRNA表达降低(P<0.01),iNOS蛋白和mRNA表达升高(P<0.01)。与模型组比较,疏肝止泻方中、高剂量组大鼠结肠黏膜中炎性细胞浸润减轻,体质量升高(P<0.01);血浆D-LA水平及血清TNF-α、IL-1β、IL-6水平降低(P<0.01);结肠组织p38、MLCK蛋白表达降低(P<0.05,P<0.01),GDNF、S100β、ZO-1蛋白和mRNA表达升高(P<0.05,P<0.01),iNOS蛋白和mRNA表达降低(P<0.01)。结论 疏肝止泻方可以降低IBS-D大鼠肠道通透性,维持肠黏膜屏障正常功能,缓解肠道炎症状态,其作用与抑制p38/MLCK信号通路活化,减少炎性因子分泌有关。
AIM To investigate the effect of Shugan Zhixie Formula on intestinal permeability of diarrheal irritable bowel syndrome(IBS-D)rats with Liver Depression and Spleen Deficiency.METHODS Fifty male Wistar rats were randomly divided into blank group,model group,pinaverium bromide group(0.0135 g/kg)and low,medium and high dose groups of Shugan Zhixie Formula(2.57,5.13,10.26 g/kg).Except the blank group,the IBS-D rat models of Liver Depression and Spleen Deficiency were established by starvation disorder+restraint tail-clamping stress+intestinal perfusion of acetic acid in the other groups.After the intervention,the morphology of colon tissue was observed by HE staining.The levels of plasma D-LA and serum TNF-α,IL-1βand IL-6 were detected by ELISA.The protein and mRNA expressions of GDNF,S100β,iNOS,ZO-1 in colon tissue were detected by Western blot and RT-qPCR.The protein expressions of p38 and MLCK in colon tissue were detected by immunohistochemistry.RESULTS Compared with the blank group,the rats in the model group had a small amount of inflammatory cell infiltration in the mucosa,and the body weight decreased(P<0.01).The levels of plasma D-LA and serum TNF-α,IL-1βand IL-6 increased(P<0.01).The protein expressions of p38 and MLCK in colon tissue increased(P<0.01),the protein and mRNA expressions of GDNF,S100β,ZO-1 decreased(P<0.01),while the protein and mRNA expression of iNOS increased(P<0.01).Compared with the model group,the infiltration of inflammatory cells in the colon mucosa of rats in the middle and high dose groups of Shugan Zhixie Formula were reduced,and the body weight was increased(P<0.01).The levels of plasma D-LA and serum TNF-α,IL-1βand IL-6 decreased(P<0.01).The protein expressions of p38 and MLCK in colon tissue decreased(P<0.05,P<0.01),the protein and mRNA expressions of GDNF,S100β,ZO-1 increased(P<0.05,P<0.01),while the protein and mRNA expression of iNOS decreased(P<0.01).CONCLUSION Shugan Zhixie Formula can reduce the intestinal permeability of IBS-D rats,maintain the normal function of intestinal mucosal barrier,and relieve the intestinal inflammatory state,which is related to inhibiting the activation of p38/MLCK signaling pathway and reducing the secretion of inflammatory factors.