西洛他唑治疗可减轻大鼠模型中野百合碱诱导的肺动脉高压。

Cilostazol therapy attenuates monocrotaline-induced pulmonary arterial hypertension in rat model.

作者信息

Chang Li-Teh, Sun Cheuk-Kwan, Sheu Jiunn-Jye, Chiang Chiang-Hua, Youssef Ali A, Lee Fan-Yen, Wu Chiung-Jen, Yip Hon-Kan

机构信息

Basic Science, Nursing Department, Meiho Institute of Technology, Pingtung.

出版信息

Circ J. 2008 May;72(5):825-31. doi: 10.1253/circj.72.825.

DOI:10.1253/circj.72.825

PMID:18441466

Abstract

BACKGROUND

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats.

METHODS AND RESULTS

Male Sprague - Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg .kg(-1 ). day(-1)) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p<0.0001). Cilostazol was given to group 2 orally on days 28-90. By day 90 following MCT treatment, the right ventricular (RV) systolic blood pressure and RV hypertrophy were significantly higher in group 1 than in groups 2 and 3 (all values of p<0.01). Additionally, connexin43 and endothelial nitric oxide synthase gene expressions of lung and RV, and Bcl-2 protein expression of RV, were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). Furthermore, the number of alveolar sac and small arterioles of the lung were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01).

CONCLUSION

Cilostazol therapy effectively attenuates of MCT-induced PAH.

摘要

背景

肺动脉高压（PAH）的特征是由于血管内皮细胞和平滑肌细胞增殖导致肺血管阻力逐渐增加，从而引起小肺动脉管腔闭塞。西洛他唑对血管内皮细胞和平滑肌细胞具有抗增殖作用，可能改善大鼠野百合碱（MCT）诱导的PAH。

方法与结果

将雄性Sprague-Dawley大鼠（每组n = 10只）随机分为仅接受MCT（75 mg/kg）的组（组1）、接受MCT加西洛他唑（20 mg·kg⁻¹·天⁻¹）的组（组2）和仅接受盐水注射的组（组3）。MCT治疗后第28天的血流动力学测量表明，MCT治疗组出现了显著的PAH（p<0.0001）。在第28 - 90天给组2口服西洛他唑。MCT治疗后第90天，组1的右心室（RV）收缩压和RV肥厚显著高于组2和组3（所有p值<0.01）。此外，组1肺和RV的连接蛋白43和内皮型一氧化氮合酶基因表达以及RV的Bcl-2蛋白表达显著低于组2和组3（所有p值<0.01）。此外，组1肺的肺泡囊和小动脉数量显著低于组2和组3（所有p值<0.01）。