基于NF-κB通路探讨从痰论治胃癌前病变胃黏膜稳态失衡的机制研究

The prevention and treatment of precancerous lesions of gastric carcinoma (PLGC) focuses on secondaryprevention in gastric cancer. The pathology of PLGC is intestinal dysplasia,which is caused by the disorder of apoptosis. Current research shows that NF-κB pathway can regulate the apoptosis and affect disease progression. It has been suggested that NF-κB pathway is directly bound up with the disorder of apoptosis.Our present study was designed to assess the contribution of phlegmcontamination(Tanzhuo) in the homeostasis imbalance on PLGC overall process, which can be treated effectively by the phlegm theory of gastric cancer. The phlegm theory of gastric cancer asserts that the tumor-phlegm microenvironment is the fundamental cause of homeostasis imbalance in Gastric Cancer,which is regarded as "Tanzhuo". Although Xiaotan Yangwei formula has been proved that it can relieve symptoms and reverse pathological condition, an molecular mechanism has not been firmly established. This study, focusing on the association between apoptosis and NF-κB pathway, was undertaken to observe the effect of Xiaotan Yangwei formula on pathological changes of gastric mucosa, the apoptotic molecule and NF-κB pathway. Moreover, the single-cell suspension of PLGC was established in vitro to investigate the effect of phlegm theory on NF-κB pathwayand cell apoptosis. The mechanism of the homeostasis imbalance based on apoptosis in PLGC may be substantial in NF-κB pathway. Our finding may demonstrate that phlegm theory of PLGC is scientific and determine the molecular mechanism and target of unblance of gastric mucosa steady state.

胃癌前病变（PLGC）的防治是胃癌二级预防的重点，其发生主要是胃黏膜细胞凋亡紊乱引起的稳态失衡所致，而NF-κB通路与细胞凋亡密切相关已为学术界所共识。我科前期研究证实从痰论治胃癌能促进胃癌细胞凋亡，认为与胃癌细胞凋亡相关的分子及信号通路可归于"痰浊"范畴，其参与了细胞凋亡紊乱所致胃黏膜稳态失衡的全过程。在此基础上进一步应用消痰养胃方从痰论治PLGC，发现可缓解临床症状逆转病理状态，但作用机制尚不明确。本项目以细胞凋亡与NF-κB通路的密切相关性为切入点，观察消痰养胃方对PLGC大鼠模型胃黏膜病理变化、NF-κB通路及其下游调控细胞凋亡相关指标的影响；同时于体外进行NF-κB信号通路阻断实验，明确该信号通路在PLGC细胞凋亡中的作用，从而阐明从痰论治PLGC对胃黏膜稳态失衡的作用靶点及分子机制，证实从痰论治PLGC思想的科学性，以期为中医药防治PLGC提供数据及理论支持。

胃癌前病变（PLGC）的防治是胃癌二级预防的重点，其发生主要是胃黏膜细胞凋亡紊乱引起的稳态失衡所致，而NF-κB通路与细胞凋亡密切相关已为学术界所共识。我科前期研究证实从痰论治胃癌能促进胃癌细胞凋亡，认为与胃癌细胞凋亡相关的分子及信号通路可归于“痰浊”范畴，其参与了细胞凋亡紊乱所致胃黏膜稳态失衡的全过程。在此基础上进一步从痰论治PLGC，发现其可缓解临床症状逆转病理状态，但作用机制尚不明确。本项目以细胞凋亡与NF-κB通路的密切相关性为切入点，体内实验建立PLGC大鼠模型，证实了从痰论治PLGC能够影响大鼠胃黏膜病理变化、NF-κB通路及其下游调控细胞凋亡相关指标；体外实验建立PLGC细胞模型，明确了阻断NF-κB信号通路能够促进PLGC细胞凋亡，从而阐明了从痰论治PLGC对胃黏膜稳态失衡的作用靶点及分子机制，证实从痰论治PLGC思想的科学性，为中医药防治PLGC提供数据及理论支持。