大鼠压力负荷性心肌肥厚与氯沙坦及赖诺普利的预防作用

Myocardial hypertrophy in pressure overload rats and the preventive effects of losartan and lisinopril

目的:探讨心血管重构的结构、生化改变及氯沙坦与赖诺普利对心血管重构的作用。方法:实验选用雄性SD大白鼠60只,随机将其分为6组:假手术组,模型组,赖诺普利20mg/(kg·d)组(大剂量赖诺普利组),赖诺普利2mg/(kg·d)(小剂量赖诺普利组),氯沙坦30mg/(kg·d)(大剂量氯沙坦组),氯沙坦5mg/(kg·d)组(小剂量氯沙坦组),每组10只。采用膈下腹主动脉缩窄法建立大鼠心肌肥厚模型。假手术组、模型组、降压和非降压剂量氯沙坦与赖诺普利在术后第2天用药至30d后,检测平均动脉压,心脏肥厚程度及局部心肌组织一氧化氮、一氧化氮合酶和胶原蛋白含量的变化。结果:模型组大鼠颈动脉平均动脉压、心脏质量、左室质量、心脏质量/体质量、左室质量/体质量,心肌细胞横径,胶原蛋白含量明显高于或大于假手术组(t=6.009～13.308,P<0.01);而局部心肌一氧化氮、一氧化氮合酶含量犤(7.04±4.11)μmol/g,(4.00±0.67)μkat/g犦明显低于假手术组犤(15.28±2.50)μmol/g,(8.17±1.00)μkat/g,t=5.416,10.966,P<0.01犦。大剂量赖诺普利组,大、小剂量氯沙坦组大鼠心肌胶原蛋白含量与假手术组比较,差异无显著性意义(P>0.05);但均明显低于模型组(t=13.011,12.206,3.302,P<0.01);大剂量氯沙坦组大鼠心肌胶原蛋白含量明显低于大剂量赖诺普利组和小剂量氯沙坦组(t=3.651,P<0.01,t=2.473,P<0.05);小剂量赖诺普利组大鼠心肌胶原蛋白含量明显低于模型组(t=4.42,P<0.01),高于假手术组(t=6.725,P<0.01)。心脏质量指数与平均动脉压呈显著正相关(r=0.7841,P<0.01);心脏质量指数与一氧化氮呈显著负相关(r=-7730,P<0.01);心脏质量指数与心肌胶原含量呈显著正相关(r=0.8177,P<0.01)。结论:心血管重构与血压、心脏间质成分及一氧化氮有密切关系;赖诺普利预防心肌肥厚可能是血流动力学和非血流动力学因素共同作用的结果;氯沙坦可能主要依靠非血流动力学因素抗心肌肥厚。

AIM:To investigate the structural and biochemical changes of cardiovascular remodeling and examine the preventive effects of lisinopril and losartan. METHODS:Sixty male SD rats were randomly divided into 6 groups with 10 rats in each:sham operated group,model group,large and small dosage(20 and 2 mg/kg per day)lisinopril groups, large and small dosage(30 and 5 mg/kg per day) losartan groups.Rat models of myocardial hypertrophy were produced by abdominal aortic coarctation.The mean arterial pressure,the changes of myocardial hypertrophic degree,nitric oxide,nitric oxide synthase and collagen of local myocardium in the sham operated group,model group,hypotensive and sub hypotensive dose groups of lisinopril and losartan.Lisinopril and losartan were given from the second day after operation for thirty days. RESULTS:Compared with the sham operated group,carotid mean arterial pressure,left ventricular mass, heart mass/body mass,left ventricular mass/body mass(left ventricular mass index),transverse diameter myocytes and collagen protein in the model group were obviously higher or larger than those in the sham operated group(t=6.009 to 13.308,P< 0.01),the contents of nitric oxide and nitric oxide synthase [(7.04± 4.11) μ mol/g,(4.00 ± 0.67) μ kat/g] of local myocardium were markedly lower than those in the sham operated group[(15.28± 2.50) μ mol/g,(8.17± 1.00) μ kat/g](t=5.416,10.966,P< 0.01).The contents of myocardial collagen in the large dose lisinopril group, large and small dosage losartan groups were insignificantly different from that in the sham operated group(P >0.05),but all obviously lower than that in the model group(t=13.011,12.206,3.302,P< 0.01),and it was markedly lower in the large dosage losartan group than in the large dosage lisinopril group and small dosage losartan group(t=3.651,P< 0.01,t=2.473,P< 0.05),while that in the small dosage lisinopril group was remarkably lower than that in the model group(t=4.42,P< 0.01) and higher than that in the sham operated group(t=6.725,P< 0.01).Left ventricular mass index was significantly and positively correlated with mean arterial pressure and content of collagen respectively(r=0.784 1, r=0.817 7,P< 0.01),but it had significant negative correlation with nitric oxide content(r=- 0.773 0,P< 0.01). CONCLUSION:Cardiovascular remodeling has intimate correlations with blood pressure,cardiac mesenchymal components and nitric oxide.The preventive effect of lisinopril on myocardial hypertrophy may be the synergistic action of hemodynamic stress and non hemodynamic stress factors,while the effect of losartan against myocardial hypertrophy is mainly depends on non emodynamic stress factors.