匹伐他汀对野百合碱诱导大鼠肺动脉高压的作用及机制研究

摘要/Abstract

摘要：

目的: 探讨他汀类药物在防治肺动脉高压中的作用及其可能的机制。方法:50只雄性SD大鼠随机均分为5组，分别为空
白对照组、模型对照组、匹伐他汀预防组（1 mg/（kg·d））和匹伐他汀高剂量（3 mg/（kg·d））治疗组、低剂量（1 mg/（kg·d））治疗组。除对照组外其余各组均通过皮下注射野百合碱诱导大鼠形成肺动脉高压。8周后对各组生存率、平均肺动脉高压（mPAP）
等进行比较及对肺小动脉中血小板源性生长衍生因子-B（PDGF-B）、Rac1mRNA的表达及IL-6分泌水平的比较。结果:预防
组、空白组大鼠均存活，肺动脉高压形成之后匹伐他汀治疗能改善生存率（P＜0.01）；匹伐他汀治疗组相比模型组能降低mPAP
（P＜0.05），下调肺小动脉PDGF-B表达、IL-6的分泌及抑制Rac1基因表达（P＜0.05）。结论:匹伐他汀防治肺动脉高压可能是
通过对Rac1基因和PDGF-B表达的调节以抑制肺动脉平滑肌细胞增殖和抑制炎症介质IL-6等机制来实现的。

关键词: 肺动脉高压, 野百合碱, 匹伐他汀, 血管平滑肌

Abstract:

Objective: To investigate effects and mechanism of pitavastatin on monocrotaline（MTC）- induced pulmonary artery
hypertension in rats. Methods: 50 male Sprague-Dawley rats were randomly divided into five groups: pulmonary arterial hypertension group, normal control group, pitavastatin prevention group（1 mg/（kg·d））, low-dose pitavastatin treatment group（1 mg/（kg·d））and highdose pitavastatin treatment group（3 mg/（kg · d））. Pulmonary arterial hypertension was induced by a subcutaneous injection of monocmtaline in rats of all groups except for the control group. After 8 weeks, survival rates and mean pulmonary arterial pressure（mPAP）among all groups were compared. The expression levels of platelet-derived growth factor-B（PDGF-B）and Rac1mRNA,secretion of IL-6 in small pulmonary artery were also detected. Results: All rats in the prevention group and normal control group survived and pitavastatin improved survival（P<0.01）. Pitavastatin in both prevention and treatment groups significantly lowered mPAP（P<0.05）, and also inhibited PDGF-B expressions and IL-6 secretion（P<0.05）, and inhibited Rac1mRNA expressions（P<0.05）. Conclusion: The effect of pitavastatin's reducing monocrotaline-induced pulmonary arterial hypertension in rats might result from the inhibition of expressions of PDGF-B and Rac1mRNA and inhibition of smooth muscle cell proliferation and inflammatory mediator IL-6．

Key words: pulmonary arterial hypertension, monocrotaline, pitavastatin, vascular smooth muscle

中图分类号:

R965

周述博，张本斯. 匹伐他汀对野百合碱诱导大鼠肺动脉高压的作用及机制研究[J]. J4, 2015, 14(2): 16-20.

Zhou Shubo, Zhang Bensi. A Study of Effects and Mechanism of Pitavastatin on Monocrotaline-induced Pulmonary
Arterial Hypertension in Rats[J]. J4, 2015, 14(2): 16-20.

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