Effect Of Fasudil On Proliferation Of Pulmonary Artery Smooth Muscle Cells In Rats With Pulmonary Hypertension

Objective: To establish the model of pulmonary hypertension in rats by the leftlung resection and monocrotaline injection, and to explore the impact of Rhokinase selective inhibitor fasudil on pulmonary vascular smooth muscle cellproliferation in pulmonary hypertensive rats.Methods: Animal model of pulmonary hypertension was established by Theleft lung resection and1%Monocrotaline (60mg/kg) subcutaneous injection onthe neck back. Healthy male SD rats were randomly divided into4groups:control group (without any treatment), model group (left lung resection andmonocrotaline-injection) and drug intervention group [fasudil (2mg/kg.d-1)intervention at the7thday after left pneumonectomy], the drug reversed group[fasudil (2mg/kg.d-1) intervention at the14thday after left pneumonectomy].With the polygraph recorder to detect mean pulmonary arterial pressure mPAP,calculate the heart of RV/(LV+S) ratio; Ki67, MCM2, p27Kip1and SM-α-actinimmunohistochemistry staining, and detecting its expression in the lung tissue;Western Blot detection of the lung tissue P27Kip1of expression was detected inrat model of pulmonary vascular remodeling.Results:(1) Comparison of weight change before and after the experiment: atotal of48rats42survived to the end of the35days of drug intervention. Therats reduced activity, shortness of breath, the tongue mucosal cyanosis,hepatomegaly performance on the28thday after injection of MCT Phyllodoce. And ultimately, there were five dead rats in model group and one in reversedgroup. Compared with control group, the weight gain of model group ratsgradually decreased (P<0.01); the weight gain of rats in the intervention groupand therapeutic group significantly increased than that of model group (P<0.05),and the intervention group increased more obviously (P＜0.05).(2) On the35thday, the mPAP, RV/(LV+S) ratio, Percentage of media thickness (WT%) ofrats treated with left lung resection and MCT injection increased significantly,compared with control group. The mPAP, RV/(LV+S) ratio, Percentage ofmedia thickness (WT%) of rats treated with left lung resection and MCTinjection decreased remarkably after fasudil administration, and the interventiongroup decreased more obviously.（3）Compared with control group, theexpression of SM-α-actin, Ki67, MCM2, cyclin B1and cyclin E1protein inmodel group increased significantly; compared with model group, theexpression of SM-α-actin, Ki67, MCM2, cyclin B1and cyclin E1in fasudilintervention group and reversing group decreased in varying degrees, and theintervention group decreased more obviously（.4）Immunohistochemical methodand Western blot testing results showed that，compared with the control group,the expression of P27Kip1protein in model group decreased; compared with themodel group, the expression of P27Kip1protein in fasudil intervention group andreversing group increased in varying degrees, and the intervention groupincreased more obviously.Conclusion:1.The Fasudil inhibit pulmonary vascular smooth muscleproliferation in left lung resection and monocrotaline-induced pulmonary hypertensive rats.2.Expression of P27Kip1protein reduced in the model groupshowed that Rho kinase signaling pathway may be involved in cell cycleregulation to promote pulmonary vascular smooth muscle cell proliferation，fasudil may be inhibit ROCK to participate raised p27kip to inhibit pulmonaryartery smooth muscle cell proliferation of pulmonary hypertensive rats.3.Fasudil can relieve or block pulmonary vascular remodeling in PAHeffectively.