小檗碱对腹泻型肠易激综合征大鼠肠屏障功能、炎症反应及NF-kB p65的影响  

Effect of berberine on the intestinal barrier function,inflammatory response and NF-kB p65 in rats with diarrhea-predominant irritable bowel syndrome

作　　者：赵义红 王菲[2] 娄静[2] ZHAO Yihong;WANG Fei;LOU Jing(Henan Medical College Hospital Workers,Zhengzhou,Henan,451191 P.R.China;The Affiliated Hospital of Henan Province Chinese Medicine Research Institute,Zhengzhou,Henan,450004 P.R.China)

机构地区：[1]河南医学高等专科学校附属医院,河南郑州451191 [2]河南省中医药研究院附属医院,河南郑州450004

出　　处：《华西药学杂志》2019年第6期592-596,共5页West China Journal of Pharmaceutical Sciences

基　　金：河南省教育厅科学技术研究重点项目(编号:17A360029)

摘　　要：目的探讨小檗碱干预腹泻型肠易激综合征(IBS-D)内脏高敏感性大鼠的机制及对肠屏障功能的影响。方法将60只大鼠随机分为正常组、模型组、阳性组及小檗碱低、中、高剂量组,采用4%乙酸灌肠复合慢性心理应激法制备IBS-D内脏高敏感性模型;空白组和模型组大鼠ig给予0.9%氯化钠溶液,小檗碱低、中、高剂量组分别ig给予小檗碱20、60、100 mg·kg^-1,阳性对照组ig给予匹维溴铵。检测大鼠的粪便含水率、腹壁撤退反射(AWR)评分和血清5-羟色胺(5-HT)、P物质(SP)、降钙素相关基因肽(CGRP)、二胺氧化酶(DAO)、D-乳酸、分泌性免疫球蛋白(SlgA)、白细胞介素-1β(IL-1β)、IL-4、IL-10、IL-17、肿瘤坏死因子α(TNF-α)等的含量。分别采用ELISA法和Western blot法检测肠黏膜NF-kB p65 DNA结合活性及其蛋白的表达水平。结果与正常组比较,模型组大鼠的粪便含水率升高,AWR评分升高,血清5-HT、SP、CGRP、DAO、D-乳酸、IL-1β、IL-17、TNF-α的水平显著升高,血清SlgA、IL-10的水平显著降低,NF-kB p65 DNA结合活性及其蛋白的表达显著升高;与模型组比较,阳性组和小檗碱各剂量组大鼠的粪便含水率降低,AWR评分降低,血清5-HT、SP、CGRP、DAO、D-乳酸、IL-1β、IL-17、TNF-α的水平显著降低,血清SlgA、IL-10的水平显著升高,NF-kB p65 DNA结合活性及其蛋白的表达显著降低。结论小檗碱可能通过降低血清5-HT、SP、CGRP的水平而改善IBS-D大鼠的内脏高敏感性;还可能通过抑制大鼠肠道被激活的NF-kB信号转导通路,提高抗炎细胞因子的表达,降低致炎细胞因子的表达,进而改善肠道炎症反应,改善IBS-D大鼠肠屏障功能。OBJECTIVE To study the mechanism of berberine on the visceral hypersensitivity and intestinal barrier function in rats with diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS The rats were randomly divided into normal group,model group,berberine group and positive group.IBS-D with visceral hypersensitivity modle was established by 4%acetic acid enema and chronic psychological stress.The rats in normal group and model group were intragastrically administrated with normal saline,and the rats in berberine group were intragastrically administrated with berberine(20 mg·kg^-1,60 mg·kg^-1 and 100 mg·kg^-1),and the rats in positive group was intragastrically administrated with pinaverium bromide.The fecal moisture percentage,abdominal withdrawal reflex(AWR)scores,5-HT,SP,CGRP,DAO,d-lactate,SIgA,IL-1β,IL-4,IL-10,IL-17 and TNF-αin serum were detected.The NF-kB p65 DNA binding activity and protein expression were detected by modified ELISA and Western blot.RESULTS Compared with the normal group,the fecal moisture percentage,AWR scores,5-HT,SP,CGRP,DAO,D-lactate,IL-1β,IL-17 and TNF-αin serum,the NF-kB p65 DNA binding activity and protein expression of model group increased significantly,while SlgA and IL-10 in serum of model group decreased significantly.Compared with the model group,the fecal moisture percentage,AWR scores,5-HT,SP,CGRP,DAO,D-lactate,IL-1β,IL-17 and TNF-αin serum,the NF-kB p65 DNA binding activity and protein expression of berberine group decreased significantly,while SlgA and IL-10 in serum of berberine group increased significantly.CONCLUSION Berberine has an effect to improve the visceral hypersensitivity of IBS-D,it is probably a result of decreasing 5-HT,SP and CGRP in serum.The activated NF-kB signal transduction pathway may be controlled by berberine on the rats with IBS-D.Berberine can improve the expression of anti-inflammatory cytokines and reduce the expression of inflammatory cytokines.Berberine have effect on IBS-D through regulating intestinal barrier function.

关 键 词：腹泻型肠易激综合征 内脏高敏感性 小檗碱 脑肠肽 肠黏膜屏障 肠屏障功能 炎症反应 NF-kB p65 

分 类 号：R96[医药卫生—药理学]