中文摘要
慢性萎缩性胃炎(CAG)有癌变倾向,阻断或逆转其发展是降低胃癌发生率的有效措施。本项目拟从PTEN启动子高甲基化是发生癌前病变的关键环节之一为切入点,应用组织形态学、现代分子生物学和限制性酶切甲基化测序(RRBS)高通量测序技术结合生物信息学分析,旨从PTEN启动子甲基化修饰异常、PI3K/Akt/mTOR信号通路的负性调控角度,探讨PTEN启动子高甲基化对CAG胃黏膜的PI3K、Akt、mTOR表达异常的调控机制。 拟从动物实验和临床试验方面,证实艾灸可能是通过降低PTEN启动子甲基化水平,参与调控胃黏膜组织的PI3K/Akt/mTOR信号通路,有效控制CAG的胃黏膜损伤,达到防治CAG癌前病变的目的,以期为针灸防治CAG癌前病变研究提供科学的实验依据。
英文摘要
As Chronic Atrophic Gastritis(CAG)has the neoplastic potential of Gastric cancer,so blocking and reversing its’ progression are effective measures to reduce the incidence of Gastric cancer.There are two goals of our research program.First,investigate the regulatory mechanism of PTEN promoter methylation to the abnormal expression of PI3K、Akt、mTOR,which are located in Gastric mucosa.In order to do this ,we want to take “High PTEN promoter methylation is a key link in the process of precancerous lesions” as the breakthrough point,regard the PTEN promoter methylation modification abnormalities and the negative regulation of PI3K/Akt/mTOR signaling pathways as the departure angles,combine histomorphology, modern molecular biology and RRBS high-throughput sequencing technologies with Bioinformatics analysis technologies.Second ,based on the clinical and basic results, we are going to prove that moxibustion can reduce the level of PTEN promoter methylation,and regulate the signaling pathways , of PI3K/Akt/mTOR,then control the Gastric mucosa damage effectively and eventually achieve the purpose of preventing and controlling CAG precancerous lesions..Based on these two goals ,we intend to supply scientific experimental basis for the extensive applications of acupuncture and moxibustion to CAG .
