西地那非对肺动脉高压大鼠肺动脉压影响的作用机制探讨

Effect of sildenafil on pulmonary artery pressure in rats

目的：探讨西地那非对肺动脉高压大鼠肺动脉压的影响，初步探讨其作用机制。方法清洁级SD雄性大鼠60只，随机分为G0、G1、G2、G3组，每组15只。G1、G2、G3组大鼠分别一次性腹腔注射MCT 60 mg/kg，诱导制作肺动脉高压动物模型，第2天开始G2组西地那非2 mg/kg灌胃，每天1次；G3组自第5周开始西地那非2 mg/kg灌胃，每天1次；G1组予等量生理盐水灌胃；G0组为空白对照组，给予生理盐水一次性腹腔注射后第2天开始每天生理盐水灌胃。腹腔注射后采用彩色多普勒超声仪测大鼠右心室横径、三尖瓣反流速度、肺动脉压、射血分数（ EF值）、缩短分数（ FS值），每周1次，共检测4周，分析数据；随后处死大鼠，取心脏、肺组织病理切片对比观察。结果 G0组大鼠肺动脉压无明显改变，G1、G2、G3组肺动脉压进行性增高，G1组更为明显。各组大鼠右心室横径逐渐增大，但G1-G3组较G0组更明显（ P﹤0.01）；G0组大鼠各时期的三尖瓣反流速度、肺动脉压无明显改变，而G1-G3组逐渐增高（P﹤0.01）。G1组大鼠肺组织病理切片可见中小动脉中膜明显增厚和小动脉肌化，部分肺组织远端小动脉闭塞，肺泡内可见心衰细胞，右室心肌细胞肥大伴纤维组织增生，G2组大鼠肺动脉仅出现轻度新生内膜病变，心脏组织病理切片无明显改变；G3组大鼠肺动脉可见较明显新生内膜病变，心脏组织病理切片可见明显炎细胞浸润。结论西地那非可有效降低肺动脉高压大鼠肺动脉压，且越早应用效果越好，其机制可能是通过改善内皮功能实现的。

Objective To investigate the effects of sildenafil on pulmonary artery pressure in rats and its mechanism. Methods Sixty male SD rats were randomly divided into group G0,G1,G2 and G3, with 15 rats in each group. The rats in group G1,G2,G3 were given intraperitoneal injection of MCT 60 mg/kg,made by the animal model of pulmonary hypertension,and the rats in group G2 were given sildenafil by 2 mg/kg gavage the next day,1 time a day,the rats in group G3 were given sildenafil by 2 mg/kg gavage from the fifth week,1 time a day;group G0 was the control group,the rats received normal saline intraperitoneal injection. After intraperitoneal injection,the right ventricular transverse diameter of three rats,tricuspid regurgitation velocity,pulmonary artery pressure were detected once a week,it lasted for 4 weeks,and the data were analyzed. Then the rats were killed and the heart and lung tissue pathological section was observed. Results Pulmonary artery pressure of rats in the group G0 had no obvious change,the pulmonary arterial pressure of group G1,G2,G3 increased,and that in group G1was more obvious. Right ventricular transverse diameter of rats increased gradually,but the group G1-G3 were more obverse than that in group G0（P﹤0. 01）,the three cusp reverse flow velocity of each period,pulmonary arterial pressure did not change significantly in group G0,while that in the G1-G3 group increased gradually （P﹤0. 01）. The lung tissue of rats showed pathological visible small arteries and arterioles muscle membrane thickening,part of the distal lung arteries occlusion,visible heart failure cell alveolar,right ventricular myocardial cell hypertrophy and hyperplasia of fibrous tissue in group G1,and the pulmonary artery of rats in the G2 group only showed mild neointimal lesions,heart tissue pathological changed not obviously;pulmonary artery of rats in group G3 showed obvious neointimal lesion,cardiac histopathology showed obvious inflammatory cell infiltration. Conclusions Sildenafil can effectively reduce the pulmonary artery pressure in rats by improving the endothelial function,and the sooner the better application effect.