川芎嗪对大鼠缺血心肌线粒体NO及自由基的影响

Effects of ligustrazine on NO and free radicals of mitochondria in rats with myocardial ischemia

目的 :研究川芎嗪抗大鼠心肌缺血损伤的机制。方法 :大鼠随机分对照组 ,造模缺血组和川芎嗪保护组。采用皮下注射异丙肾上腺素 ,造成心肌缺血损伤模型 ;采用HE染色法观察心肌组织病理学损伤 ;观测心肌线粒体中超氧化物岐化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -PX)及一氧化氮合酶 (NOS)活力 ;测定心肌线粒体丙二醛 (MDA)、Ca2 +及一氧化氮 (NO)含量。结果 :川芎嗪可明显减轻受损心肌的变性坏死反应和减少炎性细胞浸润 ;川芎嗪保护组心肌线粒体SOD、GSH -PX活力较缺血组均有显著性升高 (P <0 .0 1或P <0 .0 5 ) ,而NOS活力、Ca2 +、MDA及NO含量明显降低 (P <0 .0 1或P <0 .0 5 )。结论 :川芎嗪对大鼠心肌缺血损伤有保护作用 ,其机制可能是 :抑制线粒体钙超载 ,降低线粒体NOS活力从而减轻NO所致的损伤 ,清除自由基 ,减少脂质过氧化物的生成。

Objective:To study the mechanism of ligustrazine against myocardial ischemia in rats.Methods:The rats were randomly devided into the control,model and ligustrazine treated groups.The model of myocardial ischemia was induced by subcutaneous injection of isoproterenol(ISP,5mg/kg)into rats and by the same dose 24 hours later.Histopathological changes in myocardium was observed.The activities of superoxide dismutase(SOD),glutathion peroxidase(GSH-PX),nitric oxide synthase (NOS) and contents of malondialdehyde(MDA),Ca 2+ and nitric oxide(NO) in the myocardial mitochondria were observed respectively.Results:Ligustrazine could lighten obviously the reaction of denaturation and mecrosis and leukocytes infiltration in rat myocardium damaged by isoproterenol.In the ligustrazine treated group,as compared with those of the model,the activities of SOD、GSH-PX in the myocardial mitochondria increased significantly( P <0.01 or P <0.05),while the activity of NOS and the content of Ca 2+ 、MDA and NO decreased significantly( P <0.01 or P <0.05).Conclusions:Ligustrazine has protective effects on myocardial ischemia injury in rats,which is due to its inhibiting calcium overload,decreasing the activity of NOS and protecting myocardial mitochondria from injury which is caused by NO,scavenging free radicals and anti-lipid peroxydation reaction. Author's address:1.Department of Pharmacy,Jiangxi Medical College,Nanchang 330006,China;2.Department of Biochemistry and Molecular Biology,Jiangxi Medical College,Nanchang 330006,China