PTEN-PI3K-Akt-mTOR-自噬与凋亡交互介导胃粘膜萎缩机制及安胃汤的拮抗效应

项目名称： PTEN-PI3K-Akt-mTOR-自噬与凋亡交互介导胃粘膜萎缩机制及安胃汤的拮抗效应

项目编号： No.81460713

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 黄贵华

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 慢性胃炎→胃黏膜萎缩→肠化→异型增生→胃癌是肠型胃癌形成的公认模式。细胞凋亡与细胞增殖失衡是其主要机制。但对慢性胃炎→胃黏膜萎缩→肠化过程病变机制阐释不明。我们假说：细胞自噬与凋亡共同介导了胃黏膜萎缩的病理过程，在细胞自噬与凋亡失控后细胞过度增殖真正诱导了肠化及异型增生。本课题从PI3K-Akt-mTOR通路激活下游Beclin1，Bcl-2等介导细胞自噬与凋亡交互作用(cross-talk)的角度，复制慢性萎缩性胃炎大鼠模型，并体外细胞培养，运用现代生物学技术Western Blot，ELISA，免疫组化法检测PTEN、PI3K，Akt，mTOR，Beclin1，Bcl-2等蛋白表达变化，透射电镜观察胃粘膜超微结构改变，流式细胞仪检测细胞凋亡，探讨细胞自噬与凋亡交联介导萎缩性胃炎的胃粘膜萎缩机制及临床疗效确切的安胃汤对其的拮抗效应，为中药防治慢性萎缩性胃炎提供客观依据。

中文关键词： 中医脾胃；安胃汤；细胞自噬；凋亡；慢性萎缩性胃炎

英文摘要： The Chronic Gastritis → gastric atrophy → intestinal metaplasia → dysplasia → gastric cancer is the accepted mode of intestinal type gastric cancer. Apoptosis and cell proliferation imbalance is its main mechanism.But it was unknown to the mechanism of The Chronic Gastritis → gastric atrophy → intestinal metaplasia.So Our hypothesis is: autophagy and apoptosis jointly mediated pathological process of gastric atrophy, and which was really induced intestinal metaplasia and dysplasia ,after autophagy and apoptosis runaway cell proliferation . Beclin1 from the PI3K-Akt-mTOR pathway mediating autophagy, such as Bcl-2 mediating apoptosis which activates downstream of their cross-talk, Our subject will copy chronic atrophic gastritis rat model and in vitro cell culture, use modern biology techniques Western Blot, ELISA, immunohistochemistry method detect the expression of PTEN, PI3K, Akt, mTOR, Beclin1, Bcl-2 and other proteins change, transmission electron microscopy observe the ultrastructural changes of gastric mucosa, ad flow cytometry detect apoptosis,Coimmunoprecipitation detect Beclin1 in Bcl-2 protein, so as to explore the interaction between the them.We will explore the mechanism of autophagy and apoptosis cross-talk which mediates atrophic gastritis gastric mucosal atrophy and Investigate antagonistic effects of AnWeiTang, so we provide an objective basis for traditional Chinese medicine in prevention of chronic atrophic gastritis.

英文关键词： TCM spleen and stomach;AnWeiTang;autophagy;apoptosis;chronic atrophic gastritis