三仁汤对慢传输型便秘大鼠治疗作用及对MAPK/NF-κB信号通路影响  

Therapeutic Effect of Sanren Decoction(三汤)on Slow Transit Constipation in Rats and the Effect of MAPK/NF-κB Signal Pathway

作　　者：曹文斌 周晗 刘洋 张博 张国志 CAO Wenbin;ZHOU Han;LIU Yang;ZHANG Bo;ZHANG Guozhi(Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,Hebei,China)

机构地区：[1]华北理工大学附属医院,河北唐山063000

出　　处：《辽宁中医药大学学报》2023年第9期24-28,F0003,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：河北省中医药类科研计划项目(2021172)。

摘　　要：目的探究三仁汤对慢传输型便秘(STC)大鼠的治疗作用及对丝裂原活化蛋白激酶(MAPK)/核因子κB(NF-κB)信号通路的影响。方法SD大鼠随机分为正常组、模型组、莫沙必利组(2.5 mg/kg)、三仁汤低剂量组(8.2 g/kg)、三仁汤高剂量组(16.4 g/kg)、三仁汤+MAPK通路抑制剂(U0126)组(16.4 g/kg三仁汤+0.1 mg/kg的U0126),每组16只。除正常组外,其余5组建立STC大鼠模型,各组给予相应药物处理2周。给药结束后,活性炭混悬液灌胃,记录大鼠首次排出黑便的时间,测量肠道长度与碳墨推进距离,计算肠道传输率;酶联免疫吸附法检测血清中炎性因子水平;观察结肠黏膜组织病理学变化,检测结肠黏膜组织中水通道蛋白(AQP)4、AQP3以及结肠组织MAPK/NF-κB信号通路相关蛋白表达。结果与正常组比较,模型组大鼠结肠黏膜组织结构被破坏,腺体数量减少,细胞排列紊乱,出现明显充血、水肿,首次排出黑便的时间明显延长(P<0.05),血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,结肠黏膜组织中AQP4、AQP3表达,结肠组织中磷酸化ERK(p-ERK)/细胞外信号调节激酶(ERK)、磷酸化JNK(p-JNK)/c-Jun氨基末端激酶(JNK)、磷酸化p38MAPK(p-p38MAPK)/p38MAPK蛋白比值和NF-κB蛋白表达明显升高(P<0.05),肠道传输率明显降低(P<0.05)。与模型组比较,莫沙必利组与三仁汤各剂量组大鼠结肠黏膜病变减轻,首次排出黑便的时间明显缩短(P<0.05),血清IL-6、TNF-α水平,结肠黏膜组织中AQP4、AQP3表达,结肠组织中p-ERK/ERK、p-JNK/JNK、p-p38MAPK/p38MAPK蛋白比值和NF-κB蛋白表达明显降低(P<0.05),肠道传输率明显升高(P<0.05)。三仁汤高剂量组大鼠上述变化优于三仁汤低剂量组(P<0.05)。U0126可增强三仁汤高剂量对STC大鼠的改善效果(P<0.05)。结论三仁汤可能通过抑制MAPK/NF-κB信号通路的表达,下调AQPs的表达,改善肠道蠕动,恢复肠道传输功能。Objective To explore the therapeutic effect of Sanren Decoction(三仁汤)on slow transit constipation(STC)rats and its effect on mitogen activated protein kinase(MAPK)/nuclear factorκB(NF-κB)signal pathway.Methods SD rats were randomly divided into normal group,model group,mosapride group(2.5 mg/kg),Sanren Decoction low(8.2 g/kg),high(16.4 g/kg)dose groups,Sanren Decoction+MAPK pathway inhibitor(U0126)group(16.4 g/kg Sanren Decoction+0.1 mg/kg U0126),16 in each group.Except for normal group,STC rat model was established in other 5 groups,and each group was treated with corresponding drugs for 2 weeks.At the end of administration,gavage with activated carbon suspension and record the time of first excretion of black stool in rats,measure the length of intestine and the distance of carbon ink advance,and calculate the intestinal transmission rate;the levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assay;the histopathological changes of colonic mucosa were observed,and the expressions of aquaporin(AQP)4,AQP3 in colonic mucosal tissue and proteins related to MAPK/NF-κB signaling pathway in colonic tissue were detected.Results Compared with the normal group,the colonic mucosa structure of the model group was destroyed,the number of glands was reduced,the cell arrangement was disordered,and obvious congestion and edema appeared,the time for first discharge of black stool was significantly prolonged(P<0.05),the serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),the expressions of AQP4 and AQP3 in colonic mucosal tissues,the protein ratio of phosphorylation ERK(p-ERK)/extracellular signal regulating kinase(ERK),p38MAPK and the protein expression of NF-κB in colonic tissues were significantly increased(P<0.05),the intestinal transmission rate was significantly decreased(P<0.05).Compared with model group,the colonic mucosal lesions of rats in mosapride group and each dose group of Sanren Decoction were alleviated,and the time for first discharge of black stool

关 键 词：三仁汤 慢传输型便秘 丝裂原活化蛋白激酶 核因子ΚB 水通道蛋白 

分 类 号：R256.35[医药卫生—中医内科学]