匹伐他汀对野百合碱诱导大鼠肺动脉高压的作用及其机制  

Effects and Mechanism of Pitavastatin on Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

作　　者：周述博 张本斯[1] 

机构地区：[1]大理学院人体解剖教研室,大理671000

出　　处：《医药导报》2015年第5期569-573,共5页Herald of Medicine

摘　　要：目的探讨匹伐他汀在防治肺动脉高压中的作用及其可能机制。方法雄性斯泼累格·多雷(SD)大鼠50只,随机分为5组(n=10),分别为正常对照组、模型对照组、匹伐他汀预防组(1 mg·kg-1·d-1)和匹伐他汀大剂量(3 mg·kg-1·d-1)治疗组、小剂量(1 mg·kg-1·d-1)治疗组。除正常对照组外,其余4组均通过皮下注射野百合碱55 mg·kg-1,诱导大鼠形成肺动脉高压。8周后,比较各组存活率、平均肺动脉高压(m PAP)、血小板源性生长因子-B(PDGFB)、Rac1mRNA的表达及白细胞介素-6(IL-6)分泌水平。结果匹伐他汀预防组、正常对照组大鼠均存活,匹伐他汀小剂量治疗组、大剂量治疗组与模型对照组小鼠存活率分别为60.0%,80.0%,40.0%(P<0.01);与模型对照组比较,匹伐他汀治疗组m PAP均降低(均P<0.01),肺组织PDGF-B表达、IL-6分泌及Rac1基因表达均降低(均P<0.01)。结论匹伐他汀可能是通过对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IL-6分泌等机制防治肺动脉高压。Objective To investigate the effects and mechanism of pitavastatin on monocrotaline （ MTC ）-induced pulmonary arterial hypertension （ PAH） in rats. Methods A total of 50 male Sprague-Dawley rats were randomly divided into five groups （n=10 each）：pitavastatin treatment at low dose （1 mg·kg^-1·d^-1）,treatment at high dose （3 mg·kg^-1·d^-1）, pitavastatin prevention regimen （1 mg·kg^-1·d^-1）, model control group, and the normol control group. PAH was induced by applying a single subcutaneous injection of MTC（55 mg·kg^-1）in the first four groups of rats. The treatment lasted for 8 weeks. At the end of the study, survival rates and mean pulmonary arterial pressure （ mPAP ） among groups were compared. The expression levels of platelet-derived growth factor-B （ PDGF-B） and IL-6, Rac1 mRNA in small pulmonary artery were also detected. Results All rats in the prevention protocol and normal control group survived. Pitavastatin treatment improved＆amp;nbsp;survival in the treatment protocol（P〈0. 01）. The survival rate in the low dose, high dose, and model control group was 60. 0%, 80. 0%, and 40. 0%, respectively. Pitavastatin in both prevention or treatment protocol significantly lowered mPAP （P〈0. 01）. Pitavastatin also inhibited PDGF-B and IL-6 expression （P〈0. 01）,and inhibited Rac1 mRNA expression in lung tissues （P〈0. 01）. Conclusion Pitavastatin reduces mPAP in the MTC-induced PAH rat model, the mechanism of which may be related to inhibition of Rac1 expression,smooth muscle cell proliferation and inflammatory mediator IL-6.

关 键 词：匹伐他汀 野百合碱 肺动脉高压 血管平滑肌 

分 类 号：R972.6[医药卫生—药品] R965[医药卫生—药学]