基于网络药理学研究索罗西汤干预MCT诱导的大鼠肺动脉高压的作用机制

Research on the mechanism of Srolo Bzhtang intervention in MCT-induced pulmonary arterial hypertension in rats based on network pharmacology

目的基于网络药理学研究索罗西汤(SBT)干预MCT诱导的大鼠肺动脉高压(PAH)的作用机制。方法以SBT入血成分为研究对象,采用Swiss Target Prediction数据库预测其潜在靶点,绘制“入血成分-靶点”网络图,应用David平台进行GO、KEGG富集分析。用野百合碱制作PAH大鼠模型,通过血流动力学、形态学方法评价SBT的干预效果。利用Western Blot法检测肺组织中的PPAR-γ、Smad3、α-SMA、Cyclind1、P27、CDK4、BMPR2蛋白表达水平。结果GO、KEGG富集分析结果显示,SBT主要通过PPAR-γ等信号通路发挥作用。动物实验结果证实,SBT能有效降低PAH大鼠肺动脉压力并缓解肺血管重构状况。机制验证显示,SBT能够上调蛋白PPAR-γ、下调蛋白Smad3表达,抑制增殖相关蛋白Cyclin d1的表达,上调蛋白P27的表达。结论SBT通过激活BMPR2/PPAR-γ/Smad3信号通路抑制肺动脉平滑肌细胞增殖,改善肺血管重构。

Objective Research on the mechanism of Srolo Bzhtang intervention in MCT-induced pulmonary arterial hypertension in rats based on network pharmacology.Methods The Swiss Target Prediction database was used to predict potential targets of the component absorbed into the blood of SBT.The network of“component absorbed into blood-target”was constructed.The enrichment of GO and KEGG were analyzed based on the David platform.A model of PAH rat was made with monocrotaline.The intervention effect of SBT was evaluated by hemodynamic and morphological methods.Western Blotting was used to detect the protein expressions of PPAR-γ,Smad3,α-SMA,Cyclind1,P27,CDK4 and BMPR2 in lung tissue.Results The results of GO and KEGG enrichment analysis showed that SBT mainly played a role through PPAR-γsignaling pathways.The results of experimental verification in vivo confirmed that SBT could effectively reduce pulmonary artery pressure and relieve pulmonary vascular remodeling in PAH rats.Mechanism verification showed that SBT could up-regulate PPAR-γand down-regulate Smad3.Meanwhile,it could inhibit the expression of proliferation related protein Cyclin d1 and upregulate the expression of protein P27.Conclusion SBT could inhibit the proliferation of pulmonary artery smooth muscle cells and improve pulmonary vascular remodeling by activating the BMPR2/PPAR-γ/Smad3 signaling pathways.