Research Of CTGF, TGF-β1 Expression And Regulation By Fasudil In Pulmonary Hypertension Rats Model

Objectives High blood flow induced pulmonary hypertension model were established. Then investigate the changes of RVSP,Qp/Qs . and the remodeling of pulmonary artery. Expression of CTGF and TGF-β1 in pulmonary vascular investigated as well, finally we research whether fasudil, the Rho kinase inhibitor, have an protective effect on this model ,and its possible mechanism.Methods The rat model of pulmonary hypertension was established by underwent right carotid artery-external jugular vein shunt operation. 90 male wrister rats weighted 180g-200g were randomly divided into control group(C, 15rats each), shunt model group(S, 15rats each), and fasudil treated group(D,15rats each). The right ventricle systolic pressure (RVSP), the small pulmonary arterial morphologic changes in the each groups were studied with microscopy for morphometric analysis. Expression of CTGF and TGF-β1 expression were investigated by western blot and immunohistochemistry.Results 12rats and 10 rats survived in S2 and S4 group after the shunt operation, in the D2 and D4 group ,13 rats and 12 rats survived. In all shunt groups mean Qp/Qs is 2.01±0.29, mean Qp/Qs of D groups is 2.17±0.34, revealed a large shunt. In S and D groups ,RVSP increased significantly (P<0.01 in S2 S4 and D4 groups, P<0.05 in D2 group) . WT% showed that pulmonary arterial had a significantly remodeling in S2,S4 and D4 groups compared with the control group (P<0.01), in D2 group there is no significant difference. CTGF and TGF-β1 expression increased significantly in both S and D groups compared with the control group (P<0.01) . With a significant increase in Rho kinase activity compared with the control group (P<0.01) . After 4 weeks in the D2 and D4 groups which treated with fasudil revealed a lower RVSP (P <0.01 )and WT%(P<0.01 in D2 group, P<0.01 in D4 group)compared with S2 and S4 groups , CTGF and TGF-β1 expression and Rho kinase activity also decreased compared with S2 and S4 groups (P<0.01) .Conclusions CTGF,TGF-β1 are involved in the development of pulmonary hypertension. Fasudil may prevent the development of pulmonary hypertension and pulmonary vascular remodeling .and decrease CTGF, TGF-β1 expression in high flow induced pulmonary hypertension.