糖肾方治疗糖尿病肾病心肌纤维化的实验研究及网络药理学研究

Study on the effect of Tangshen Formula on myocardial fibrosis of diabetic kidney disease and the mechanism based on network pharmacology

目的:研究糖肾方治疗糖尿病肾病(DKD)心肌纤维化的作用及潜在机制。方法:采用单侧肾切除合并链脲佐菌素诱导的DKD大鼠心肌纤维化模型,糖肾方治疗20周后取心脏组织进行Masson染色;应用网络药理学方法构建糖肾方活性化合物成分-心肌纤维化潜在靶点网络,以及蛋白-蛋白相互作用网络,筛选关键靶点并进行靶点类型归属、富集分析和通路富集分析。结果:糖肾方显著减少DKD大鼠心肌胶原沉积;糖肾方含有268个化合物活性成分,对应277个心肌纤维化潜在靶点,主要调控IL6、IL4、TLR4、IL1A等炎症反应和血管生成相关基因,涉及细胞因子-细胞因子受体相互作用通路、液体剪切应力和动脉粥样硬化信号通路、肿瘤相关蛋白多糖、糖尿病并发症中的AGE-RAGE信号通路等136条通路。结论:糖肾方具有治疗DKD心肌纤维化的作用,炎症反应和血管生成相关基因可能是其关键靶点。

Objective:To explore the effect and potential mechanism of Tangshen Formula(TSF)on myocardial fibrosis of diabetic kidney disease(DKD).Methods:The DKD with myocardial fibrosis rat model induced by unilateral nephrectomy and Streptozotocin usage.After 20 weeks of treatment with TSF,cardiac tissues were taken for Masson’s trichrome staining.The network pharmacology method was used to construct the active compounds-potential target network and protein-protein interaction network of active compounds of TSF.The key targets were screened,and the targets were analyzed by gene ontology and Kyoto encyclopedia of genes and genomes pathway analysis.Results:TSF significantly reduced myocardial collagen deposition in DKD rats.There were 268 active compounds of TSF and 277 potential targets in the treatment of myocardial fibrosis.It was mainly through IL6、IL4、TLR4、IL1 A、CXCR4、VEGFA、KDR target genes,involved in 136 pathways including cytokine-cytokine receptor interaction,fluid shear stress and atherosclerosis,proteoglycans in cancer and AGERAGE signaling pathway in diabetic complications.Conclusion:TSF has the effect of treating myocardial fibrosis in DKD,and inflammation and angiogenesis related genes may be its key targets.