基于TGF-β/Smads信号通路研究欣胃颗粒防治胃癌前病变的机制

Study on Mechanism of Xinwei Granule(欣胃颗粒)Preventing and Treating Precancerous Lesion of Gastric Carcinoma Based on TGF-β/Smads Pathway

目的研究欣胃颗粒对胃癌前病变(precahcerous lesion of gastric carcinoma,PLGC)患者胃黏膜中转化生长因子β(transforming growth factor-β,TGF-β)/Smads信号通路相关蛋白TGF-β1、转化生长因子-Ⅱ型受体(transforming growth factor-βⅡreceptor,TβR-Ⅱ)、Smad4、Smad7表达水平的影响,为治疗PLGC提供中医诊疗思路和有效方案。方法将符合纳入标准的气阴两虚、夹瘀夹毒型PLGC患者60例设为疗前组,并将其随机分为欣胃颗粒组和胃复春组,分别给予口服欣胃颗粒和胃复春片,连续服用12周,另设10例浅表性胃炎患者为空白组作为对照且未予药物治疗。采用免疫组化法检测患者服药前后胃黏膜病理组织学变化和Real-time PCR方法检测各组胃黏膜组织中TGF-β1、TβR-Ⅱ、Smad4、Smad7的mRNA及蛋白表达情况。结果与空白组相比,疗前组患者TGF-β1、TβR-Ⅱ、Smad7表达升高,Smad4表达降低(P<0.05),且与空白组、欣胃颗粒组、胃复春组对比差异明显,有统计学意义(P<0.05)。欣胃颗粒组、胃复春组均可下调TGF-β1、TβR-Ⅱ、Smad7的表达,上调Smad4的表达。两组相比,欣胃颗粒组下调TGF-β1、TβR-Ⅱ、Smad7表达水平的作用明显(P<0.05),而胃复春组上调Smad4表达水平的作用明显(P<0.05)。结论欣胃颗粒能有效治疗PLGC,其机制可能与干预TGF-β/Smads通路传导,下调TGF-β1、TβR-Ⅱ、Smad7的表达,同时上调Smad4的表达有关。

Objective To investigate the effect of Xinwei Granule(欣胃颗粒,XWG)on the expression levels of transforming growth factorβ(TGF-β)/Smads pathway-related proteins TGF-β1,TGF-βtypeⅡreceptor(TβR-Ⅱ),Smad4 and Smad7 in gastric mucosa of patients with precancerous lesion of gastric carcinoma(PLGC)and provide a traditional Chinese medicine diagnosis and treatment idea and an effective plan for the treatment of PLGC.Methods Sixty PLGC patients which belonged to Qi-Yin deficiency with blood stasis and toxin type in traditional Chinese medicine,as the pre-treatment group,were randomly divided into XWG group and Weifuchun Tablet(胃复春片,WFCT)group.And the two groups were given oral XWG and WFCT respectively for 12 weeks.In addition,10 patients with superficial gastritis were set as blank group for control without medicine.The histopathological changes of gastric mucosa before and after taking the medicine were detected by immunohistochemical method,and the expressions of TGF-β1,TβR-Ⅱ,Smad4,Smad7 mRNA and proteins in gastric mucosa tissues of each group were detected by Real-time PCR method.Results Compared with those of the blank group,the expressions of TGF-β1,TβR-Ⅱand Smad7 were increased and the expression of Smad4 was decreased in the pre-treatment group(P<0.05).The differences among pre-treatment group and blank group,XWG group,WFCT group were statistically significant(P<0.05).In XWG group and WFCT group,the expressions of TGF-β1,TβR-Ⅱand Smad7 could be decreased and the expression of Smad4 could be increased.Compared with the two groups,the XWG group significantly decreased the expressions of TGF-β1,TβR-Ⅱand Smad7(P<0.05),while the WFCT group significantly increased the expression of Smad4(P<0.05).Conclusion XWG can effectively treat PLGC and its mechanism may be related to the intervention of TGF-β/Smads pathway conduction,down-regulating the expressions of TGF-β1,TβR-Ⅱand Smad7 and up-regulating the expression of Smad4.