基于网络药理学与实验验证探讨益肾化瘀方延缓肾间质纤维化机制

Mechanism of Yishen Huayu Formula in delaying renal interstitial fibrosis based on network pharmacology and experimental verification

目的:通过网络药理学探索益肾化瘀方延缓肾间质纤维化(RIF)的分子机制,并进行实验验证。方法:利用网络药理学获取益肾化瘀方延缓RIF可能的作用机制,并进行分子对接验证其结合力。构建RIF小鼠模型,观察益肾化瘀方对肾组织病理损伤以及Bax、Bcl-2表达的影响。结果:网络药理学研究显示益肾化瘀方可通过多靶点干预RIF,其作用机制可能与细胞凋亡等通路相关。分子对接显示益肾化瘀方活性成分与防治RIF共有靶点的结合活性较好。动物实验显示,益肾化瘀方可降低RIF小鼠肾组织细胞凋亡水平,改善肾小管损伤,显著降低肾组织Bax、Bcl-2表达(P<0.01),进而减轻RIF。结论:益肾化瘀方可以干预多种RIF基因,其保护作用机制可能与下调细胞凋亡有关。

Objective:To explore the molecular mechanism of Yishen Huayu Formula in delaying renal interstitial fibrosis(RIF)through network pharmacology,and to carry out experimental verification.Methods:Using network pharmacology to obtain the possible mechanism of Yishen Huayu Formula in delaying RIF,and conduct molecular docking to verify its binding force.To establish the model of RIF in mice and observe the effect of Yishen Huayu Formula on renal tissue pathological injury and expression of Bax and Bcl-2.Results:Network pharmacology studies had shown that Yishen Huayu Formula could intervene in RIF through multiple targets,and its mechanism of action may be related to pathways such as cell apoptosis.Molecular docking showed that the active components of Yishen Huayu Formula had better binding activity with common targets for prevention and treatment of RIF.Animal experiments showed that Yishen Huayu Formula could reduce the level of apoptosis of renal tissue cells,improve the damage of renal tubules,significantly reduce the expression of Bax and Bcl-2 in renal tissue(P<0.01),thereby alleviate RIF.Conclusion:Yishen Huayu Formula can interfere with a variety of RIF genes,and its renal protective mechanism may be related to the down regulation of apoptosis.