首页|参苓白术散对慢性溃疡性结肠炎小鼠经典细胞焦亡信号通路及肠道紧密连接的调控效应机制

参苓白术散对慢性溃疡性结肠炎小鼠经典细胞焦亡信号通路及肠道紧密连接的调控效应机制

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目的:探究参苓白术散对慢性溃疡性结肠炎(UC)小鼠经典细胞焦亡信号通路及肠道紧密连接的调控效应及作用机制.方法:将32只C57BU6小鼠随机分为正常组、模型组、参苓白术散组及阳性药组.采用2.5%葡聚糖硫酸钠(DSS)自由饮用,建立慢性UC小鼠模型,第15天起灌胃给药至造模结束.观察小鼠一般情况、体质量、大便性状、便血情况并计算疾病活动指数(DAI)评分,HE染色观察结肠组织病理学改变,ELISA法检测结肠组织炎症因子白细胞介素(IL)-1β、IL-18含量,Western Blot检测结肠组织紧密连接闭锁小带蛋白1(ZO-1)、闭合蛋白(Occludin)及细胞焦亡NLRP3、GSDMD-N、c-caspase-1蛋白表达.结果:与正常组比较,模型组小鼠结肠长度显著缩短(P<0.01),DAI评分上升,结肠组织可见大片弥漫性炎症细胞浸润,黏膜层坏死脱落严重,组织病理学评分显著升高(P<0.01),结肠组织炎症因子IL-1β、IL-18含量显著增高(P<0.01),ZO-1、Occludin蛋白表达显著下降(P<0.01),NLRP3、GSDMD-N、c-caspase-1蛋白表达显著上升(P<0.01).与模型组比较,参苓白术散组结肠长度显著增长(P<0.05),DAI评分下降,结肠组织病理学评分显著降低(P<0.05),结肠组织IL-1β、IL-18含量显著下降(P<0.01),ZO-1、Occludin蛋白表达显著上升(P<0.01),NLRP3、GSDMD-N、c-caspase-1蛋白表达显著下降(P<0.01).与阳性药组比较,参苓白术散组结肠组织NLRP3、c-caspase-1蛋白表达显著降低(P<0.01,P<0.05),Occludin蛋白表达显著升高(P<0.01).结论:参苓白术散具有防治慢性UC的作用,其机制可能与调控结肠组织经典细胞焦亡信号通路及肠道紧密连接,减少炎症因子表达有关.
Regulatory effect mechanism of Shenling Baizhu Powder on canonical pyroptosis pathway and intestinal tight junction in mice with chronic ulcerative colitis
Objective:To explore the regulatory effect and mechanism of Shenling Baizhu Powder(SLBZS)on canonical pyroptosis pathway and intestinal tight junction in mice with chronic ulcerative colitis(UC).Methods:Thirty-two C57BL/6 mice were randomly divided into control group,model group,SLBZS group and 5-ASA group.The mice were administered 2.5%dextran sulfate sodium salt(DSS)in daily drinking to induce chronic UC,and were given the corresponding drugs by intragastric administration from the 15th day.The general condition,body weight,stool characteristics and stool blood of mice were observed,and the DAI score was calculated.The histopathological changes of colon were observed by HE staining.The contents of inflammatory cytokines IL-1β and IL-18 in colon tissue were detected by ELISA.The protein expression of tight junction ZO-1,Occludin,and the cell pyroptosis NLRP3,GSDMD-N and c-caspase-1 in colon tissue were detected by Western Blot.Results:Compared with the control group,colon length of the model group was significantly shortened(P<0.01),DAI score was increased,inflammatory cells were infiltrated in colon tissue,and the mucosal layer was necrotic and exfoliated seriously,the histopathological score was significantly increased(P<0.01),the contents of inflammatory cytokines IL-1β and IL-18 in colon tissue were significantly increased(P<0.01),the protein expression of ZO-1 and Occludin were significantly decreased(P<0.01),the protein expression of NLRP,GSDMD-N and c-caspase-1 were significantly increased(P<0.01).Compared with the model group,colon length of SLBZS group was lengthened(P<0.05),DAI score was decreased,the histopathological score was decreased(P<0.05),the contents of inflammatory cytokines IL-1 β and IL-18 were significantly decreased(P<0.01),the protein expression of ZO-1 and Occludin were significantly increased(P<0.01),the protein expression of NLRP3,GSDMD-N and c-caspase-1 were significantly decreased(P<0.01).Compared with 5-ASA group,the protein expression of NLRP3 and c-caspase-1 in colon tissue of SLBZS group were significantly decreased(P<0.01,P<0.05),the protein expression of Occludin was significantly increased(P<0.01).Conclusion:SLBZS has the effect of preventing and treating chronic UC,and its mechanism is related to the regulation of colon tissue canonical pyroptosis pathway and intestinal tight junction,and reduction of inflammatory factors expression.

Shenling Baizhu PowderUlcerative colitis(UC)PyroptosisTight junctionMechanismInflammatory factors

夏瑜彬、王晓柠、刘馨烛、谢凌云、王甲璇、卢曼晨、戚莉、刘佳、王振宜

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上海中医药大学附属岳阳中西医结合医院,上海 200437

上海中医药大学交叉科学研究院中医方证基础研究中心,上海 201203

上海市中医药研究院肝病研究所,肝肾疾病病症教育部重点实验室,上海 201203

参苓白术散 溃疡性结肠炎 细胞焦亡 紧密连接 机制 炎症因子

国家自然科学基金面上项目

82274531

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(7)
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