养阴活胃合剂对慢性萎缩性胃炎大鼠PI3K/Akt信号通路的影响

Effect of Yangyin Huowei mixture on PI3K/Akt signaling pathway in rats with chronic atrophic gastritis

关键词:  养阴活胃合剂  慢性萎缩性胃炎  PI3K/Akt信号通路  胃黏膜  增殖和凋亡

Key words:  Yangyin Huowei Mixture  chronic atrophic gastritis  PI3K/Akt signaling pathway  gastric mucosa  proliferation and apoptosis

摘要:

[目的] 探讨养阴活胃合剂对慢性萎缩性胃炎（CAG）模型大鼠磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（PKB/Akt）信号通路的影响。[方法] 将清洁级别SD大鼠利用随机数字法分为空白组与造模组，造模组采用N-甲基-N′-硝基-N-亚硝基胍（MNNG）以及饥饱失常法等多因素造模，造模成功后分组，养阴活胃合剂干预8周。给药结束后，苏木精-伊红（HE）染色观察胃组织病理变化；实时荧光定量（RT-qPCR）检测胃黏膜中PI3K、Akt1、mTOR、p53 mRNA表达情况；蛋白免疫印迹法（WB）检测胃黏膜中PI3K、Akt1、mTOR、p53蛋白表达情况。[结果] 与空白组比较，模型组大鼠胃黏膜出现萎缩、并伴有轻度肠化；PCR结果表明PI3K、Akt1、mTOR、p53 mRNA表达量明显升高（P＜0.01）；WB结果表明PI3K、Akt1、mTOR、p53蛋白表达量明显升高（P＜0.01）。与模型组比较，养阴活胃合剂各剂量组及维酶素组大鼠的胃黏膜萎缩明显改善；PCR结果表明PI3K、Akt1、mTOR、p53 mRNA表达量明显降低（P＜0.05或P＜0.01）；WB结果表明PI3K、Akt1、mTOR、p53蛋白表达量明显降低（P＜0.05）。[结论] 养阴活胃合剂能下调PI3K、Akt1、mTOR、p53蛋白及mRNA的表达，有效改善CAG模型大鼠胃黏膜的病理状况，该方能够调控细胞增殖与凋亡反应，起到治疗CAG的作用。

Abstract:

[Objective] To investigate the effect of Yangyin Huowei Mixture on phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB/Akt) signaling pathway in rats with chronic atrophic gastritis(CAG).[Methods] Sixty SD rats of clean grade were divided into blank group(n=10) and model group(n=50) by random number method. The model group was modeled by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and abnormal hunger and satiety. After successful modeling,the rats were divided into groups and intervened by Yangyin Huowei Mixture for 8 weeks. After administration,the pathological changes of gastric tissue were observed by hematoxylin-eosin(HE) staining. The expression of PI3K,Akt1,mTOR and p53 mRNA in gastric mucosa was detected by real time fluorescence quantitative(RT-qPCR). The expression of PI3K,Akt1,mTOR and p53 protein in gastric mucosa was detected by Western blot(WB).[Results] Compared with the blank group,the gastric mucosa of rats in the model group showed atrophy and mild intestinal metaplasia. The results of PCR showed that the expression of PI3K,Akt1,mTOR and p53 mRNA was significantly increased(P<0.01). WB results showed that the expression of PI3K,Akt1,mTOR and p53 protein was significantly increased(P<0.01). Compared with the model group,the gastric mucosal atrophy of the rats in the Yangyin Huowei Mixture groups and the Weimeisu group were significantly improved. The results of PCR showed that the expression levels of PI3K,Akt1,mTOR and p53 mRNA were significantly decreased(P<0.05 or P<0.01). WB results showed that the expression of PI3K,Akt1,mTOR and p53 protein was significantly decreased(P<0.05).[Conclusion] Yangyin Huowei Mixture can down-regulate the expression of PI3K,Akt1,mTOR,p53 protein and mRNA,and effectively improve the pathological condition of gastric mucosa in CAG model rats. This prescription can regulate cell proliferation and apoptosis,and play a role in the treatment of CAG.