补阳还五汤调控细胞自噬改善HPH肺血管重构的机制研究OA

Objective To investigate the mechanism by which Buyang Huanwu Decoction(补阳还五汤,BHD)improves pulmonary vas-cular remodeling in hypoxic pulmonary hypertension(HPH)through regulating autophagy.Methods Sixty SPF male SD rats were ran-domly divided into a blank control group,a model group,a sildenafil group,and low-,medium-,and high-dose BHD groups,with 10 rats in each group.Except for the blank control group,the HPH model was established in the other groups using the normobaric intermit-tent hypoxia method,and corresponding drug interventions were administered simultaneously.The right ventricular systolic pressure(RVSP)and right ventricular hypertrophy index(RVHI)were detected;pulmonary vascular structure was observed by HE staining;the protein expressions of Beclin-1,ATG5,P62,PCNA and PI3K/AKT/mTOR signaling pathway-related proteins were detected by West-ern Blot and RT-PCR.Results Compared with the blank control group,the RVSP and RVHI in the HPH model group were significantly increased,the pulmonary arteriole wall was thickened with an elevated muscularization rate,the expressions of PCNA,PI3K,AKT and mTOR were up-regulated,the expressions of Beclin-1 and ATG5 were up-regulated,and the expression of P62 was down-regulated(P<0.01).Compared with the model group,all the above indicators were significantly improved in each BHD group and the sildenafil group,and the effect of BHD was dose-dependent(P<0.01).Conclusion BHD can activate autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway,reduce the excessive proliferation of pulmonary artery smooth muscle cells,and thereby improve pulmonary vascular remodeling in HPH.