Mechanism Of Ventriettlar Remodeling In Rat With The Pulmonary Artery Hypertension

Objective:To establish a practical animal model with pulmonary artery hypertension(PAH), to detect hydroxyproline-. myocardial collagen fibers; osteopontin> integrin (33 with pulmonary artery hypertensive rats, to approach mechanism of ventriettlar remodeling in rat with the pulmonary artery hypertension.Methods:To establish a practical animal model with pulmonary artery hypertension(PAH).60 SD rats randomly divided into 5 groups.12 in each group, A control group and 4 experimental pulmonary artery hypertension (PAH), At 4 time points (MCT injection after the first week 1,2,3,4) take samples. MCT will be injected 1,2,3,4 weeks after experimental pulmonary artery hypertension (PAH),the corresponding experimental group were referred to as PAH1, PAH2, PAH3 and PAH4 experimental group. Myocardial hydroxyproline determination, myocardial Masson staining and Ⅰ/Ⅲ collagen immunohistochemistry methods were determined in order to detect collagen fibers. The right ventricle myocardial osteopontin (OPN) and integrin β3 (receptor of OPN) mRNA expression levels were detected by RT-PCR method at different time points in rats in each group. The right ventricle myocardial osteopontin (OPN) and integrin β3 protein expression levels were detected by immunohistochemistry andWestern blot method at different time points in rats in each group.Results:(1)Cardiac hypertrophy and symptom of right heart failure such as hydrothorax, ascites and congestive liver cirrhosis were observed in the end-staged PAH rats. In comparison to the control smPAP and RV/(LV+S) weremarklyelevated [(38.20±3.32)vs(15.08±2.13)mmHg,P<0.001],[(0.49±0.012)vs(0.28±0.016), P<0.01]; the density of pulmonary vessels was greatly reduced[(3.69±0.13)vs (7.66±0.25)/mm2, P<0.01], that indicating a well formation of PAH. (2)In addition, muscularization of pulmonary arterioles as well as hypertrophy of tunica media was observed in the right lung specimens. Myocardial hydroxyproline content increased in pulmonary artery hypertension group, compared with the control group there was a significant difference (P<0.01) in pulmonary artery hypertension group. Image analysis showed that myocardial collagen fiber area increased significantly in pulmonary artery hypertension group. (3) In control group, OPN of and integrin β3 mRNA expression level in the right ventricle myocardial of rats is very low, and pulmonary artery hypertension in each group (PAH1-4), (4) OPN and integrin β3 expression in the right ventricle myocardial of rats were significantly increased. Compared with the control group, there was a significant difference in each group (PAH1-4)(P<0.05). OPN and integrinβ3 protein expression levels increased in right ventricular myocardial of pulmonary artery hypertension group, their expression levels have increased along with the extension of the time with pulmonary artery hypertension. Compared with the control group, differences were significant in pulmonary artery hypertension group (P<0.05). Correlation analysis showed that between the right ventricle myocardial OPN mRNA expression and right ventricular hypertrophy index was positively correlated (r= 0.728, P<0.01). Between the right ventricle myocardial integrin P3 mRNA expression and right ventricular hypertrophy index was positively correlated (r= 0.722, P<0.01).Conclusion:pulmonary artery hypertension effect ventriettlar remodeling process, the express of hydroxyproline、myocardial collagen fibers^osteopontin and integrin P3 was important contribution;...