摘要
目的探讨地尔硫卓和贝那普利对野百合碱诱发的肺动脉高压大鼠肺动脉重构的影响。方法雄性SD大鼠40只,体质量200～230g,分为对照组(一次性腹腔注射1mL生理盐水)、肺动脉高压组、地尔硫卓组和贝那普利组(后3组一次性腹腔注射野百合碱40mg/kg)。4周后,地尔硫卓组和贝那普利组分别给予地尔硫卓25mg/(kg.d)和贝那普利10mg/(kg.d)灌胃治疗,对照组和肺动脉高压组给予相同体积生理盐水,持续4周。待药物干预满4周后,分别测定大鼠的肺动脉平均压(MPAP)、右心室肥厚指数(RVHI)、肺小动脉管壁厚度占管径的百分比(WT%)及管壁面积占血管总面积的百分比(WA%)。留取大鼠的肺动脉干,并采用Western-Blot法测定各组大鼠肺动脉电压门控性钙离子通道α1c亚基(Cavα1c)、肌浆网钙ATP酶2a亚基(SERCA-2a)及3型兰尼碱受体(RyR3)蛋白的表达。结果与对照组比较,肺动脉高压组MPAP[(36.1±4.2)比(23.2±3.3)mmHg]、RVHI[(45.6±3.8)%比(25.6±2.9)%]、WT%[(58.5±4.6)%比(37.6±3.6)%]、WA%[(76.8±7.0)%比(51.4±6.4)%]和Cavα1c表达均明显升高(均P<0.05)。与对照组比较,肺动脉高压组SERCA-2a表达明显减弱,RyR3表达明显增多(均P<0.05)。与肺动脉高压组比较,经地尔硫卓或贝那普利治疗后大鼠的MPAP、RVHI、WT%、WA%和Cavα1c表达水平均明显降低(均P<0.05)。结论地尔硫卓和贝那普利可以通过调节肺动脉高压大鼠肺动脉钙离子通道的表达来改善肺小动脉重构。
Objective To evaluate the effects of diltiazem and benazepril on monocrotaline-induced pulmonary arterial remodeling in rats.Methods Forty Sprague-Dawley rats were randomly assigned into four groups：normal control（Ctr）,pulmonary arterial hypertension（PAH）,diltiazem（Dil）and benazepril treated group（Ben）.The rats were given a dose of 40 mg/kg monocrotaline intraperitoneally in PAH,diltiazem and benazepril treated groups and untreated rats were given 1 mL NS intraperitoneally as control.After 4 weeks,the rats were given 25 mg/（kg·d）of diltiazem or 10 mg/（kg·d）of benazepril by gavage respectively in diltiazem or benazepril treated group for 4 weeks.4 weeks after medication,mean of pulmonary arterial pressure（MPAP）and right ventricular hypertrophy index（RVHI）were measured,and WT% and WA% of pulmonary arterioles were evaluated.The protein analysis for Cavα1c,SERCA-2a and RyR3 in pulmonary artery was evaluated by Western-Blot.Results Compared with Ctr group,MPAP [（36.1±4.2）vs（23.2±3.3）mm Hg],RVHI [（45.6±3.8）% vs（25.6±2.9）%],WT% [（58.5±4.6）% vs（37.6±3.6）%],WA% [（76.8±7.0）% vs（51.4±6.4）%] and Cavα1c expression were significantly increased in PAH（P0.05 respectively）.Compared with Ctr group,SERCA-2a expression was downregulated and RyR3 expression was upregulated in PAH（P0.05 respectively）.After administration of diltiazem or benazepril,MPAP,RVHI,WT%,WA% and Cavα1c expression were significantly reduced（P0.05 respectively）.Conclusion Diltiazem,as effective as benazepril,may regress the remodeling of pulmonary arterioles,which could be through the regulation of calcium channels expression in pulmonary artery in monocrotaline-induced pulmonary arterial hypertensive rats.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2011年第7期636-641,共6页
Chinese Journal of Hypertension
基金
福建省自然科学基金资助项目(C0540010和2008J0082)
关键词
肺动脉高压
地尔硫卓
贝那普利
钙离子通道
重构
Pulmonary arterial hypertension
Diltiazem
Benazepril
Calcium channel
Remodeling
