Rho激酶抑制剂法舒地尔对肺动脉高压大鼠内皮素-1水平的干预研究

目的 探讨Rho激酶抑制剂法舒地尔对肺动脉高压(PH)大鼠内皮素-1水平的干预作用.方法 32只成年Wistar大鼠均分为对照3周组(C3)、PH模型3周组(P3)、6周组(P6)及干预组(F组).予野百合碱建模,第22日始F组予法舒地尔腹腔内注射干预.C3、P3、P6、F组大鼠分别于造模后3、6周末测定大鼠右心室收缩压(RVSP)、血浆内皮素-1 (ET-1)水平,观察肺小动脉病理.结果 ①C3、P3、P6、F组大鼠RVSP分别为(31.2±7.6)、(43.3±8.3)、(56.9±6.9)、(47.3±6.3)mmHg.血浆ET-1分别为(1.09±0.39)、(1.83±0.29)、(2.34±0.65)、(1.90±0.33)ng·mL-1 ;②造模后大鼠RVSP、ET-1随时间延长而升高,法舒地尔干预后上述指标明显下降.③造模后肺小动脉平滑肌增殖,管腔狭窄,F组较P6组管腔明显增大,增殖减轻；④RVSP与ET-1存在明显正相关(r=0.721,P＜0.01).结论 Rho激酶抑制剂法舒地尔能显著降低PH大鼠血浆ET-1水平,有效降低肺动脉压力.

Effect of Rho kinase inhibitor on plasma ET-1 fasudil on pulmonarly hypertension in rat with pulmonary hypertension

Objective To investigate the effect of Rho kinase inhibitor fasudil on plasma ET-1 in rats with pulmonary hypertension.Methods A total of 32 Wistar rats were divided into a control group(C3),a PH3 and PH6 week model group(P3,P6) and an F group(F)(n=8).MCT solution was used to create the PH models.Group F were treated with fasudil.The right ventricle systolic pressure(RVSP),plasma ET-1,and small pulmonary arterial morphometry were measured.Results ① The RVSP in group C3,P3,P6 and F was(31.2±7.6),(43.3±8.3),(47.3±6.3)and(56.9±6.9)mmHg;and ET-1 was(1.09±0.39),(1.83±0.29),(2.34±0.65) and(1.90±0.33)ng·mL-1;② The RVSP and ET-1 were the highest in group P6,followed by group F,P3,and C3.③ Pathematological assessment showed that the PH rat model engendered vascular remodeling,and significantly decreased in group F when compared with group P6.④ The level of plasma ET-1 was positively associated with RVSP(r=0.721,P<0.01).Conclusion Rho kinase inhibitor can decrease the level of ET-1 and improve the MCT-induced PH.