The Expression And Function Of Autophagy-related Proteins In Monocrotaline-induced Pulmonary Artery Hypertension

Objective:To explore the possible role of autophagy in initiation and developme nt of pulmonary hypertension by detecting dynamic expressions of autophagy related p roteins in animal model of pulmonary hypertension.Method:The animal model of pulmonary hypertension was established by injecting monocrotaline(MCT) into SD rats of doses of 60 mg/kg. After three weeks, rats were sacrificed and the followings were measured: ① Right ventricular systolic pressure(RVS P); ② pulmonary vascular morphology by HE staining; ③ dynamic m RNA expressio n of autophagy related genes LC3 and p62 byseal-time quantitative PCR; ④ dynamic ex pre-ssion of autophagy related proteins LC3 and p62 in pulmonary hypertension mode l rats by immunohistochemistry and Western blot.Results:Compared with normal control group(CON group),① RVSP were increased gradually along with the extension of time in the model group(P<0.05); ② the thickeness of pulmonary arteriolar wall increased obviously with hyalinization in model group, indicating the vessel lomen narrowing and occlusion,and endometrial fibrosis and pulmonary vascular remodeling emergenced, the normal structure of small blood vessels disappeared along with fibrinoid exudation, around the blood vessels there was a large number of inflammatory cell infiltration; ③ the m RNA expression of LC3 in MCT grou p showed an increasing trend whethers the p62 m RNA expression decreased with the ex t-ension of time.④The average IOD at different time points of LC3 in model group wer e significantly increased whethers the expressions of p62 protein were decreased.Conclusion: Monocrotaline can successfully induce pulmonary hypertension in SD rats.The dynamic expression of autophagy related protein markers in initiation and development of pulmonary hypertension suggested that autophagy may be involved in the pathogenesis of PAH.