氧自由基在一氧化氮缺乏所致高血压及心血管重构中的作用  

Oxygen free radicals in hypertension and cardiovascular remodeling induced by nitric oxide-deficiency

作　　者：吴延庆[1] 陈琦[1] 程晓曙[1] 吴清华[1] 苏海[1] 李菊香[1] 邹斌[1] 

机构地区：[1]江西医学院心血管病研究所江西医学院第二附属医院心内科,南昌330006

出　　处：《临床心血管病杂志》2004年第7期416-419,共4页Journal of Clinical Cardiology

基　　金：江西省自然科学基金资助项目 (No :0 0 4 0 0 4 5 )

摘　　要：目的 :通过观察抗氧化剂Ebselen的干预效果 ,探讨氧自由基 (OFR)在一氧化氮 (NO)缺乏所致高血压、心血管重构中的作用。方法 :将 2 4只Wistar大鼠随机分为 3组 ,每组 8只 :①C组 :正常对照组 ;②L组 :L NAME 5 0mg·kg-1·d-1;③L +E组 :L NAME 5 0mg·kg-1·d-1加Ebselen 30mg·kg-1·d-1。隔周测动脉收缩压 ;8周末处死大鼠采集标本 ,检测血浆、心尖部心肌匀浆组织中NO含量及心肌超氧阴离子 (O-2 )水平、血管紧张素Ⅱ一型受体 (AT1受体 )表达 ;取心脏作病理形态检测。结果 :①L组血压逐渐升高 :自 1周末起 ,对比C组同期血压差异均有统计学意义 (P <0 .0 5 )。Ebselen干预早期对血压升高无明显影响 ,但在 8周末则明显低于L组 (P<0 .0 5 ) ;②L组心肌组织NO水平明显低于C组 ,L +E组则明显高于L组 ;③L组心肌O-2 、AT1受体表达水平 ,明显高于C组 ,L +E组则明显低于L组 ;④L组及L +E组心脏重量 /体重 (HW /BW )较对照组有显著增高 ;L +E组较L组有下降趋势 ,但P >0 .0 5。左室壁厚度L组及L +E组均较C组明显增高 (P <0 .0 5 ) ,而Ebselen干预后其左室壁厚度则明显变薄 (P <0 .0 5 ) ;心肌小动脉壁厚 /腔径比值的变化 :L组明显较对照组为大 ,L +E组与L组比较则此种比值有所减小 ,但L +E组仍较对照组为高 (PObjectives: To investigate the effects of ebselen, a kind of anti-oxidative drug, OFR in hypertension and cardiovascular remodeling induced by Nitric oxide-deficiency.Method:Twenty-four Wistar rats were randomly divided to three groups: C group (Control group), L group (L-NAME 50 mg·kg -1·d -1), L+E group (L-NAME 50 mg·kg -1·d -1 +Ebselen 30 mg·kg -1·d -1). Systolic blood pressure (SBP) were measured every two weeks. After 8-weeks, the rats were killed. Then their blood and hearts were collected. The levels of NO in plasma and myocardium of apex were measured. The production of superoxide anion and the levels of AT 1 receptor expression in myocardium were also determined. The rest of heart were processed morphology analysis. Result: ①There was a time-dependent elevation of SBP in L group compared with that in control group after 1 week (P< 0.05). Ebselen did not affect the blood pressure during the early period, but an obviously decrease of blood pressure was deserved at the end of 8th week (P< 0.05). ② The level of Nox of myocardium in L group was decreased Companed with that in C group, Ebselen increased the level of NOx of myocardium. ③ The levels of O 2- production and the expression of AT 1 receptor in myocardium were increased in L group compared with that in C group. but they were lower in L+E group. ④After L-NAME treatment, the ratio of heart weight-body weight (HW/BW) markedly increased in L and L+E group. The thickness of left ventricle showed an increase, which was alleviated by Ebselen significantly. Ebselen decreased the ratio of thickness to lumen diameter in little artery which were induced by L-NAME. Conclusion: Ebselen, an anti-oxidative drug, enable to attenuate the development of hypertension and cardiovascular remodeling in NO-deficient rats. OFR may accelerates the formation of hypertension and cardiovascular remodeling.

关 键 词：氧自由基 高血压 心血管重构 一氧化氮 

分 类 号：R544.1[医药卫生—心血管疾病]