氧化苦参碱对心肌损伤大鼠线粒体保护作用的研究

Investigation about protective effects of oxymatrine on myocardial mitochondria injury in rats

目的:探讨氧化苦参碱(oxymatrine,OMT)对异丙基肾上腺素(isoproterenol,ISO)致心肌损伤大鼠线粒体(mitochondria,Mit)的保护作用及其机制。方法:健康雄性SD大鼠24只,随机分为4组:对照组、模型组、OMT低、高剂量组,每组6只。皮下注射ISO5 mg.kg-1.d-1复制心肌损伤模型,低、高剂量组分别腹腔注射OMT100,150 mg.kg-1.d-1,连续10 d。差速离心法提取心肌Mit,比色法测定血浆乳酸(lactic acid,LD)、丙二醛(malondi-aldehyde,MDA)的含量与乳酸脱氢酶(lactic dehydrogenase,LDH)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)的活性和心肌Mit中MDA的含量与琥珀酸脱氢酶(succinicdehydrogenase,SDH),SOD,GSH-PX的活性,原子吸收法测定心肌Mit的钙含量。HE染色观察心肌组织的病理学改变,电镜下观察Mit超微结构的改变。结果:与模型组相比,低、高剂量OMT均可减轻心内膜下心肌缺血性损伤,保护心肌Mit超微结构的完整性,且二者均可显著降低心肌线粒体MDA和钙含量(P<0.01),增加线粒体SOD与GSH-PX活性(低剂量组P<0.05,高剂量组P<0.01),升高SDH活性(P<0.01),降低血浆LDH活性(P<0.01)和LD含量(低剂量组P<0.05,高剂量组P<0.01)。结论:OMT可保护ISO致心肌损伤大鼠Mit的结构和功能,其机制可能与抑制脂质过氧化、减轻钙超载、改善心肌细胞的代谢有关。

Objective： To study the protective mechanism of oxymatrine （OMT） on myocardial mitochondria injury in rats induced by isoproterenol （ISO）. Method： Twenty-four male Sprague-Dawle rats were randomly divided into 4 groups： normal, model. Low and high dosage oxymatrine treated groups, with 6 rats in each group. The myocardial injury model was induced by subcutaneous injection of ISO 5 mg · kg^-1· d^-1. The low and high therapy groups were intraperitoneal injected with oxymatrine 100, 150 mg · kg^-1· d^-1 respectively for 10 days. Differential centrifugation method was used to extract myocardial mitochondria. Plasma malondialdehyde （ MDA）, lactic acid （LD）, lactic dehydrogenase （ LDH）, superoxide dismutase （ SOD）, glutathione peroxidase （GSH-PX） and myocardial mitochondria MDA, succinic dehydrogenase （SDH）, SOD, GSH-PX were measured respectively by means of colourimetry. Calcium content in myocardial mitochondria was measured by atom absorptive spectrophotography. Hematoxylin-eosine staining showed the morphology changes of myocardium, myocardial mitochondria ultrastructure changes were observed under the transmission electron microscope. Result： Compared with model group, myocardial mitochondria injury was ameliorated and the integrity of mitochondria ultrastructure was protected when rats were treated with low and high dosage oxymatrine, which could decrease MDA and calcium contents in myocardial mitochondria obviously （P 〈0.01 ） , and increase SOD, GSH-PX activites （low dosage group P 〈0. 05, high dosage group P 〈 0, 01 ） and SDH activity （ P 〈 0. 01 ）, respectively. Besides, they also decreased LDH activity （ P 〈 0.01 ） and LD content （low dosage group P 〈 0. 05, high dosage group P 〈 0. 01 ） respectively in plasma. Conclusion： OMT has cardioprotective effects against myocardial mitochondria injury by inhibiting the lipid peroxidation, attenuating the calcium overload and improving the myocardial cell metabolism.