Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Department of Ophthalmology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Clin Hemorheol Microcirc. 2019;71(1):3-8. doi: 10.3233/CH-160232.
This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH).
Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups.
MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced.
Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.
本研究旨在探讨 Rho 激酶抑制剂法舒地尔对缺氧性肺动脉高压（HPH）大鼠内皮素-1（ET-1）和一氧化氮（NO）表达的影响。
将 24 只雄性 SD 大鼠随机分为三组：对照组、模型组（HPH 组）和 HPH+法舒地尔组。采用常压间歇性缺氧（IH）建立大鼠 HPH 模型。观察各组大鼠平均肺动脉压（mPAP）、右心室肥厚指数（RVHI）、ET-1 和 NO 水平以及肺血管结构变化。
与对照组相比，HPH 组 mPAP、RVHI 和 ET-1 水平明显升高，NO 水平明显降低；与 HPH 组相比，HPH+法舒地尔组 mPAP、RVHI 和 ET-1 水平明显降低。在 HPH 组中，ET-1 水平与 mPAP 和 RVHI 呈显著正相关，NO 与 mPAP 和 RVHI 水平呈负相关，ET-1 水平与 NO 水平呈显著负相关。在 HPH 组中，肺小动脉壁普遍增厚，管腔狭窄明显；而法舒地尔治疗后，肺小动脉壁增厚和狭窄程度明显减轻。
法舒地尔可显著降低 HPH 大鼠 ET-l 水平，增加 NO 水平，抑制肺动脉高压的发展。
