苦参碱对阿霉素诱导大鼠心肌损伤的保护作用及其机制研究

目的研究苦参碱对阿霉素诱导大鼠心肌损伤的保护作用及其机制。方法 SD大鼠随机分为对照组、模型组和苦参碱25、50、100 mg/kg组,每组各20只。模型组大鼠ip注射用阿霉素2.5 mg/kg,1次/周,连续给药6周,累积剂量15 mg/kg,建立心肌损伤模型。对照组ip等量生理盐水。苦参碱组造模前2 d ip注射用苦参碱25、50、100 mg/kg,连续给药5 d。观察大鼠心肌细胞病理学,采用酶联免疫吸附法检测大鼠血清线粒体偶联因子CF6水平,应用分光光度法测定Na~+-K~+-ATP酶、Ca2~+-ATP酶活力,采用试剂盒检测谷胱甘肽过氧化物酶(GSH-px)、总超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果苦参碱各组心肌组织肿胀,肌束间、间质有灶性出血现象显著减轻。与模型组比较,苦参碱各组血清CF6水平显著降低(P0.05);线粒体Na~+-K~+-ATP酶、Ca2~+-ATP酶活性显著升高(P0.05);心肌组织GSH-px活性及SOD活力升高,MDA含量显著降低(P0.05)。结论苦参碱能保护阿霉素引起的大鼠心肌损伤,其作用机制与改善线粒体ATP酶活性、降低线粒体偶联因子6水平、减轻氧化应激水平有关。

Protection of matrine against cardiac injury induced by doxorubicin in rats and its mechanism

Objective To study the protective effects of matrine against cardiac injury induced by doxorubicin in rats and explore its mechanism. Methods SD rats were randomly divided into control group, model group, and matrine (25, 50, and 100 mg/kg) groups, and each group had 20 rats. Rats in model group were ip administered with Adriamycin Injection 2.5 mg/kg, once per week, cumulative reach to 15 mg/kg, and treated for 10 d to establish cardiac injury model. Rats in control group were ip administered with equivalent normal saline. Rats in the matrine groups were ip administered with Matrine for injection 25, 50, and 100 mg/kg 2 d before models were established, and treated for 5 d. Pathological changes of cardiac muscle cells in rats were observed. The serum levels of CF6 were detected by enzyme-linked immunosorbent assay, and activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase were detected by electromicroscope. Activities of GSH-px and SOD, and contents of MDA were determined by corresponding kits. Results Myocardial tissue swelling, muscle and interstitial hemorrhage in the matrine groups were significantly reduced. Compared with the model group, serum levels of CF6 in the matrine groups were significantly decreased (P < 0.05), and activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase in mitochondrion of the matrine groups were significantly increased (P < 0.05). Compared with the model group, activities of GSH-px and SOD in myocardial tissue of the matrine groups were significantly increased, contents of MDA were significantly decreased (P< 0.05). Conclusion Matrine has protective effects against cardiac injury induced by doxorubicin in rats, whose mechanism may be related to improvement of activities of Na⁺-K⁺-ATPase and Ca²⁺-ATPase, reduction of CF6 levels, and release of oxidative stress levels.