雷米普利对肺动脉高压大鼠肺血管平滑肌细胞的增殖和重构的影响

Effects of Ramipril on Proliferation of the Pulmonary Vascular Smooth Muscle Cells and PulmonaryVascular Remodeling Induced by Monocrotaline in Rats

目的探讨雷米普利对野百合碱(monocrotaline,MCT)诱导的肺动脉高压大鼠肺血管平滑肌细胞的增殖和重构的影响.方法雄性SD大鼠30只,随机分为:正常对照组、MCT组、MCT+雷米普利组.后两组颈部注射MCT60mg/kg后,用雷米普利灌胃4周.对照组颈部注射生理盐水后,用生理盐水灌胃4周.测定大鼠的右室收缩压(RVSP)和心室重量变化,测定肺小动脉管壁厚度(WT)占动脉外径(ED)的百分比(WT%)及管壁面积(WA)占血管总面积的百分比(WA%).采用免疫组化比较肺血管平滑肌细胞(VSMC)α-平滑肌肌动蛋白(α-actin)及增殖细胞核抗(PCNA)的阳性表达.结果MCT组与正常对照组相比,RVSP、右心室(RV)/左心室加室间隔(LV+S)、RV/体重(BW)、(LV+S)/BW、WT%、WA%、PCNA阳性率显著升高,MCT+雷米普利组上述指标低于MCT组.MCT组与正常对照组相比α-actin染色IOD值显著降低,而MCT+雷米普利组与MCT组相比α-actin染色IOD值显著升高.结论在MCT诱导的肺动脉高压模型中,雷米普利抑制肺血管平滑肌细胞由收缩表型向合成表型转化,抑制平滑肌细胞的增生,减缓肺血管重构进程.

Objective To investigate the therapeutic effect of ramipril on proliferation of the pulmonary vascular smooth muscle cells and pulmonary vascular remodeling induced by MCT in rats.Methods Thirty SD rats were randomly divided into three groups：control group,MCT group and MCT＋ Ramipril group.The rats in the latter two groups were injected 60 mg/kg of MCT subcutaneously and then received Ramipril in drink water for 4 weeks.The rats in control group were injected saline subcutaneously first and then received normal drink water.Right ventricular systolic pressure（RVSP）was measured.The animals＇ hearts were measured to calculate the ratio of right ventricle to left ventricle plus septum（RV/LV＋S,right ventricle mass to body weight（RV/BW）and left ventricle plus septum mass to body weight（LV＋S/BW）.Percentage of wall thickness（WT%）and percentage of wall area（WA%）of pulmonary arterioles were evaluated.Immunohistochemical stains were used to identifyα-actin and proliferation cells nuclear antibody（PCNA）distribution in pulmonary arteries.Restults After four weeks,these parameters of RVSP,RV/（LV＋S）,RV/BW,（LV＋S）/BW,WT % and WA %,the positive ratio of PCNA in MCT group were significantly increased compared with control group.However,the above parameters were dramatically decreased in MCT＋ Ramipril group.Compared with control group,α-actin IOD was lower in MCT group,while it was dramatically increased in MCT＋ Ramipril group.Conclusion Ramipril can prevent the development of pulmonary arterial hypertension induced by MCT and inhibit pulmonary vascular remodeling by inhibiting the proliferation of pulmonary vascular smooth muscle cells.