益气活血法对MNNG诱导萎缩性胃炎癌前病变大鼠hedgehog信号通路的调控作用

Regulation effects of invigorating qi and activating blood therapy on the hedgehog signal pathway in rats with precancerous lesions of atrophic gastritis

目的探讨益气活血法对萎缩性胃炎癌前病变大鼠hedgehog信号通路的调控影响。方法雄性Wistar大鼠随机分为空白组、模型组、黄芪组、三七组、黄芪三七组、Purmorphamine组、环巴明组及叶酸组,运用MNNG负荷多因素法制备萎缩性胃炎癌前病变模型。应用HE染色评价胃黏膜病理损伤,应用Western Blot、RT-PCR和量子点介导的免疫荧光化学法分别检测各组大鼠胃组织hedgehog信号通路的蛋白和基因表达水平。结果与空白组相比,模型组大鼠血清PGⅠ/PGⅡ和GAS含量显著降低(P<0.01),Shh、Ptch基因及蛋白含量均明显下调(P<0.05,P<0.01),Smo蛋白表达减弱(P<0.01)。与模型组相比,三七组、黄芪三七组及Purmorphamine组PGⅠ/PGⅡ明显升高(P<0.01),黄芪组、三七组及黄芪三七组GAS含量显著升高(P<0.05)。三七组、黄芪三七组及叶酸组Shh蛋白表达明显升高(P<0.05),三七组和Purmorphamine组Ptch蛋白表达增多(P<0.05),黄芪组、三七组、黄芪三七组和Purmorphamine组Smo蛋白表达显著增强(P<0.05,P<0.01)。结论益气活血法可激活hedgehog信号通路,对萎缩性胃炎癌前病变大鼠胃黏膜病变起到改善作用。

Objective To evaluate the effects of invigorating qi and activating blood therapy on hedgehog signal pathway in rats with precancerous lesions of atrophic gastritis. Methods The model was established by MNNG,male wistar rats were randomly divided into control group,model group,Astragalus group,Panax notoginseng group,Astragalus plus Panax notoginseng group,Purmorphamine group,cyclopamine group and folic acid group. HE was used to evaluate the pathological injury of stomach. The mRNA and protein expression levels of hedgehog signal pathway were detected by RT-PCR,Western Blot analysis and immunofluorescence. Results Compared with the control group,GAS and PG I/PG II level were reduced in model group（ P〈0. 01）,the mRNA and protein expression levels of Shh and Ptch were obviously down-regulated（ P〈0. 05,P〈0. 01）; the expression of Smo protein was decreased（ P〈0. 01）. Compared with the model group,the level of PG I/PG II was increased in the Panax notoginseng group,Astragalus plus Panax notoginseng group and Purmorphamine group（ P〈0. 01）,the level of GAS was increased in the Astragalus group,Panax notoginseng group and Astragalus plus Panax notoginseng group（P〈0. 05）. The protein of Shh was increased in the Panax notoginseng group,Astragalus plus Panax notoginseng group and folic acid group（ P〈0. 05）. The protein of Ptch was markedly up-regulated in Panax notoginseng group and Purmorphamine group（ P〈0. 05）. The expression of Smo was significantly increased in Astragalus group,Panax notoginseng group and Astragalus plus Panax notoginseng group and Purmorphamine group（ P〈0. 05,P〈0. 01）. Conclusion Invigorating qi and activating blood therapy can activate hedgehog signal pathway,and can improve the gastric mucosal lesion in precancerous lesion of atrophic gastritis.