基于TGF-β/Smads信号通路探讨胃痞消逆转GPL大鼠胃黏膜EMT效应机制  

Mechanism of Weipixiao on Reversing the GPL Rat Gastric Mucosa EMT Elimination via Regulation of TGF-β/Smads Signal Pathway

作　　者：蔡甜甜[1] 潘华峰[1] 张成哲 曾晓会 赵自明 陈晓东[1] 李思怡[1] 刘伟[1] 

机构地区：[1]广州中医药大学,广东广州510405 [2]广东省中医药工程技术研究院,广东广州510095

出　　处：《中药新药与临床药理》2017年第4期424-429,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目(No.81473620)

摘　　要：目的观察健脾化瘀解毒中药复方胃痞消对胃癌前病变(GPL)大鼠TGF-β/Smads信号通路的调控效应,探讨胃痞消逆转GPL大鼠胃黏膜上皮-间质转化(EMT)的效应机制。方法采用N-甲基-N,-硝基-N-亚硝基胍(MNNG)为造模剂结合饥饱失常多因素造模方法复制GPL大鼠模型,连续26周,于16周时开始连续灌胃给药10周,分组如下:正常组,模型组,胃复春组(0.2 g·kg^(-1)),胃痞消高、低剂量(15,7.5 g·kg^(-1))组。观察大鼠胃黏膜组织病理学(HE染色)变化及超微结构;Western Blot法检测尾型同源基因家族2(CDX2)、转化生长因子二型受体(TGF-βRI)I、Rho相关激酶(RhoA)、p-Smad2、p-Smad3、神经钙黏蛋白(N-cad)、β-连环蛋白(β-catenin)表达。结果与正常组比较,模型组GPL大鼠胃黏膜CDX2、RhoA、p-Smad2、p-Smad3和N-cad蛋白表达均显著升高(P<0.05,P<0.01),β-catenin蛋白表达显著降低(P<0.05);与模型组比较,胃痞消高、低剂量组大鼠胃黏膜TGF-βRⅡ、p-Smad2、p-Smad3和RhoA表达均显著降低(P<0.05,P<0.01),胃痞消低剂量组大鼠胃黏膜CDX2表达显著降低(P<0.05),胃痞消高剂量组大鼠胃黏膜N-cad表达显著降低(P<0.01),β-catenin的表达显著升高(P<0.01)。结论胃痞消可拮抗TGF-β/Smads信号通路,进而活化诱导TGF-βRⅡ、p-Smad2、p-Smad3和RhoA表达下调,调控GPL大鼠胃黏膜EMT,延缓GPL向肿瘤的进展。Objective To explore the effects of Weipixiao （WPX） on reversing gastric mucosa epithelial mesenchymal transition （EMT） elimination in gastric precancerous lesions（GPL）rats, and the effective mechanism from the aspects of regulating the TGF-[3/Smads signal pathway. Methods Male SD rats were randomly divided into control, model, Weifuchun （WFC 0.2 g·kg^-1） , WPX high-dose （15g·kg^-1） , WPX low-dose （7.5 g·kg^-1） groups. After successfully established the GPL model, rats were consecutively administrated WPX or WFC by intragastric gavage for 10 weeks. Histopathological staining and uhrastructure of gastric mucosa of the rats were observed, and expression levels of TGF-β RII, CDX2, RhoA, p-Smad2, p-Smad3, N-cad and β-catenin in gastric mucosal epithelial cells were detected by Western Blot. Results Expression of CDX2, RhoA, p-Smad2, p-Smad3 and N-Cad in the model group increased significantly compared with the control group （P 〈 0.05, P 〈 0.01） ; expressions of TGF-βRII, p-Smad2, p-Smad3 and RhoA in the WPX groups were evidently reduced compared with the model group（P 〈 0.05, P 〈 0.01） ; expressions of CDX2 in the WPX low-dose group was notably decreased （P 〈 0.05） ; expression of N-cad in the WPX high-dose group was remarkably decreased （P 〈 0.01 ）; expression of β-catenin in the WPX high-dose group was significantly increased （P 〈 0.01 ）. Conclusion WPX can act against TGF-β/Smads signaling pathway, induce up-regulaion of TGF-β RII, p-Smad2, p-Smad3, and RhoA, and affect the GPL rat gastric mucosa epithelial mesenchymal transformation, hence prevent and cure gastric cancer.

关 键 词：胃癌前病变 胃痞消 TGF-β/Smads信号通路 上皮-间质转化 

分 类 号：R285.5[医药卫生—中药学]