环丙贝特调控Ang2/Tie通路对缺氧性肺动脉高压新生大鼠肺血管重塑的影响OA

Objective To investigate the effect of ciprofibrate on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension(HPH)by regulating the angiopoietin 2(Ang2)/tyrosine protein kinase(Tie)pathway.Methods Newborn rats were randomly separated into normal group,HPH group,low concentration ciprofibrate group,medium concentration ciprofibrate group,high concentration ciprofibrate group,and high concentration ciprofibrate+Ang2 activator rat Ang2 recombinant protein(rrAng2)group,with 12 rats in each group.Except for the normal group,newborn rats in all other groups were constructed with HPH models and administered once a day for 2 weeks starting from the first day of hypoxia.The changes in right ventricular systolic pressure(RVSP)and right ventricular hypertrophy index were detected.Hematoxylin-eosin(HE)staining was applied to detect the pathology of lung tissue and the percentage of pulmonary artery middle layer wall thickness to its outer diameter(MT),and the percentage of pulmonary artery middle layer cross-sectional area to its total cross-sectional area(MA)changes.Immunofluorescence staining was applied to detect the relative fluorescence intensity of hypoxia inducible factor-1α(HIF-1α)and endothelin-1(ET-1)in pulmonary arteries.Enzyme-linked immnosorbent assay(ELISA)was applied to detect levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-8 in pulmonary arteries.Western blot was applied to detect Ang2 and Tie2 proteins in pulmonary arteries.Results Compared with the normal group,the HPH group showed an increase in pulmonary artery wall thickness and narrowing of the lumen,the RVSP,right ventricular hypertrophy index,MA,MT,HIF-1α,ET-1 relative fluorescence intensity,TNF-α,IL-8 levels,and Ang2 and Tie2 proteins in the pulmonary artery increased(P＜0.05).Compared with the HPH group,the pulmonary artery wall thickening and luminal stenosis in rats in the low,medium,and high concentration ciprofibrate groups were improved,the RVSP,right ventricular hypertrophy index,MA,MT,HIF-lα,ET-1 relative fluorescence intensity,TNF-α,IL-8 levels,and Ang2 and Tie2 proteins in the pulmonary artery reduced(P＜0.05).Compared with the high concentration ciprofibrate group,the high concentration ciprofibrate+rr Ang2 group showed more significant thickening of the pulmonary artery wall and narrowing of the lumen in rats,the RVSP,right ventricular hypertrophy index,MA,MT,HIF-1α,ET-1 relative fluorescence intensity,TNF-α,IL-8 levels,and Ang2 and Tie2 proteins in the pulmonary artery increased(P＜0.05).Conclusion Ciprofibrate may improve pulmonary vascular remodeling in neonatal rats with HPH by inhibiting the Ang2/Tie pathway,thereby suppressing the expression of HIF-1 α and ET-1 as well as the inflammatory response.