摘要
目的:运用网络药理学及实验验证方法,分析胃痞灵调控凋亡治疗胃癌前病变(GPL)的作用机制。方法:利用网络药理学技术筛选胃痞灵治疗GPL的关键成分及作用靶标,构建成分-靶点网络,并进行蛋白相互作用分析、GO及KEGG通路富集,分析其调控细胞凋亡可能的作用机制。建立GPL小鼠模型,予以胃痞灵干预,观察用药后小鼠黏膜改变及凋亡相关蛋白Bcl-2、Bcl-xl、Bax表达变化。结果:胃痞灵中含有113个活性成分,对应GPL103个靶点,其中有36个核心蛋白,主要涉及47条GO条目与18条信号通路;体内实验证实,与模型组比较,胃痞灵可通过下调Bcl-2、Bcl-xl(P<0.01),上调Bax(P<0.05)以促进细胞凋亡,从而发挥治疗作用。结论:胃痞灵可通过调控凋亡相关蛋白表达,以发挥促凋亡作用。
Objective: To analysis mechanism of Weipiling in treatment gastric precancerous lesions(GPL) by regulating pro-apoptosis based on using network pharmacology and experimental verification methods. Methods: A network pharmacology approach was used to detect the ingredients in Weipiling and the targets of GPL. Then, compound-targets network, protein interaction network, Gene oncology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were constructed to explore the therapeutic mechanism of Weipiling regulated pro-apoptosis. Mice GPL model was established and intervened by Weipiling to observe the changes in mucosal and the expression of apoptosis-related proteins Bcl-2, Bcl-xl and Bax. Results: Weipiling had 113 active compounds corresponding to 103 targets. It had 36 core proteins, 47 GO terms and 18 pathways in treating GPL. In vivo experiments confirmed Weipiling played a therapeutic role by down-regulating Bcl-2 and Bclxl(P<0.01) and up-regulating Bax(P<0.05) to promote apoptosis. Conclusion: Weipiling could regulate apoptosis-related protein expression to play a pro-apoptosis role in the prevention and treatment of GPL.
引文
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