化痰消瘀方治疗胃癌前病变的分子机制研究  

Research on Molecular Mechanism of Huatan Xiaoyu Fang in the Treatment of Precancerous Lesion of Gastric Cancer

作　　者：崔国良 冯小可[1,2] 吴娟[1,2] 苗正月[1,2] 林贞妍 蒋金桃 魏睦新 Cui Guoliang;Feng Xiaoke;Wu Juan;Miao Zhengyue;Lin Zhenyan;Jiang Jintao;Wei Muxin(Department of Traditional Chinese Medicine,the First Affiliated Hospital with Nanjing Medical University,Nanjing 210029;Institute of Integration of Chinese and Western Medicine,Nanjing Medical University,Nanjing 210029)

机构地区：[1]南京医科大学第一附属医院中医科,南京210029 [2]南京医科大学中西医结合研究所,南京210029

出　　处：《中药药理与临床》2021年第1期172-179,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：江苏省中医药局科技项目(编号:YB2015166)。

摘　　要：目的:基于网络药理学预测和胃癌前病变(PLGC)大鼠模型验证的方法,探讨化痰消瘀方治疗胃癌前病变的分子机制。方法:利用网络药理学技术筛选化痰消瘀方治疗胃癌前病变的关键活性成分及其作用靶点,并进行蛋白质间相互作用分析,GO功能富集和KEGG通路富集。建立PLGC大鼠模型,给予化痰消瘀方干预治疗12 w,苏木精-伊红染色法观察大鼠胃黏膜组织的病理学改变,AB-PAS染色法观察大鼠胃黏膜组织的肠上皮化生病理改变,免疫组化法对预测结果中PI3K/Akt信号通路的相关蛋白表达进行分析。结果:网络药理学结果显示:化痰消瘀方含有98个活性成分,作用于129个靶点,主要涉及酶结合、药物反应、细胞凋亡调控等生物学途径以及PI3K/Akt、TNF等信号通路。动物实验验证结果显示:与模型对照组比较,化痰消瘀方干预治疗后可改善PLGC大鼠胃黏膜组织病理学改变,并减轻肠上皮化生等病理改变,PI3K/Akt信号通路中相关蛋白p-Akt、p-PI3K、mTOR表达下调,PTEN表达上调。结论:化痰消瘀方通过多成分、多靶点、多通路共同作用治疗PLGC,其中PI3K/Akt信号通路是其作用的主要通路之一。Objective: To explore the molecular mechanisms of Huatan XIaoyu Fang in the treatment of precancerous lesion of gastric cancer(PLGC) based on network pharmacology prediction and verification in PLGC model rats. Method: The key components and target of Huatan XIaoyu Fang in the treatment of precancerous lesions were screened by Network pharmacology technology, and protein-protein interaction analysis, GO function enrichment and KEGG pathway enrichment were conducted. PLGC rat model was established and treated with Huatan Xiaoyu Fang for 12 weeks. Pathological changes of gastric mucosa were observed by hematoxylin eosin staining, pathological changes of intestinal metaplasia in gastric mucosa were observed by AB-PAS staining, and the related protein expression of PI3 K/Akt signaling pathway was analyzed by immunohistochemistry. Results: Network pharmacology results showed that: Huatan Xiaoyu Fang contained 98 active components, which acted on 129 targets, mainly involving biological pathways such as enzyme binding, drug reaction, apoptosis regulation, and PI3 K/Akt, TNF signaling pathways. The animal experiments results showed: compared with the model group, after the intervention of Huatan Xiaoyu Fang, the histopathological conditon of gastric mucosa in PLGC rats was improved, and the pathological changes of intestinal metaplasia was also improved. The protein expressions of p-Akt, p-PI3 K and mTOR in PI3 K/Akt signal pathway were down-regulated, while the expression of PTEN was up-regulated. Conclusion: Huatan Xiaoyu Fang is a multi-component, multi-target and multi-channel therapy for PLGC, and PI3 K/Akt signal pathway is one of the main pathways.

关 键 词：网络药理学 化痰消瘀方 胃癌前病变 磷脂酰肌醇3-激酶 蛋白激酶B 

分 类 号：R285.5[医药卫生—中药学]