雷公藤甲素对大鼠心肌毒性的时间节律性研究  

Myocardial toxicity of triptolide on rats:the temporal rhythm effect

作　　者：关伟[1] 戴清保 胡永良[1] 张武[1] 朱建华[1] 

机构地区：[1]皖南医学院法医毒理毒化教研室,安徽芜湖241002 [2]颍上县人民法院,安徽颍上236200

出　　处：《皖南医学院学报》2010年第1期18-21,共4页Journal of Wannan Medical College

基　　金：安徽省教育厅自然科学研究基金项目(2006KJ413B)

摘　　要：目的:观察雷公藤甲素对大鼠心脏的毒性作用并探讨其时间节律性规律,为临床合理用药降低毒副反应提供实验数据和理论依据。方法:雄性SD大鼠40只随机分为4组,包括对照组(A组);雷公藤甲素早晚用药组(B组)20μg/kg,bid;雷公藤甲素早上用药组(C组)40μg/kg,qd,8am;雷公藤甲素晚上用药组(D组)40μg/kg,qd,8pm。连续灌胃7周后断头处死,用HE染色法和透射电镜法,从形态学方面探讨较长时期和不同时辰服用雷公藤甲素对大鼠心脏的毒理病理损害和毒性机制。结果:光镜下可见B组大鼠左心室心肌间质血管扩张充血,有灶性出血;C组大鼠心肌血管周围有少量淋巴细胞浸润;D组大鼠心肌未见血管扩张充血,心肌细胞间可见淋巴细胞浸润。电镜下可见B组和C组心肌有水肿,少数线粒体肿胀,嵴突破坏,肌浆网扩张;而D组心肌有轻度水肿,线粒体肿胀不明显,嵴突未见明显破坏。结论:①心脏形态学观察提示心肌对雷公藤甲素具有较高的敏感性,较长期服用雷公藤甲素对大鼠心脏具有毒性作用。②雷公藤甲素对心肌的毒性作用具有时间节律性。Objective：To observe the myocardial toxicity of triptolide on the rat by examining the temporal rhythm effect for providing the experimental data and evidence of this drug in clinical use to reduce the adverse effects. Methods ： Forty male SD rats were randomized into groups of controls （ group A）, administering triptolide at dose of 20 μg/kg, bid （ group B） ,the drug use of 40 μg/kg,qd,8am（ group C） or 40 μg/kg,qd,8pm （group D）. The animals were decapitated after 7 consecutive weeks of the drug use, and morphologically, HE staining and transmission electron microscope were used to detect the myocardial toxicity and mechanisms oftriptolide on the rat concerning the long-term or temporal drug use. Resuits ： The rats in group B were found the left ventricular interstitium with expansion and congestion and focal hemorrhage under the light microscope. Spots of lymphocytic infiltration were seen around the myocardial vessels in group C. Though absence of congestion due to vasodilatation in group D,lymphocytic infiltration was seen around myocardial cells. By electron microscope, the myocardial edema was found in both group B and C,with some swollen mitochondrial, damaged cristae and dilated sarcoplasmic reticulum. Mild myocardial edema was found in group D, but with less evident mitochondrial swelling and cristae involvement. Conclusion： Morphologic observation suggests thai myocardia may be highly responsive to triptolide. Given that the long-term use of this drug,it will lead to toxicity on the myocardium. In addition, triptolide toxicity on the myocardium depends on the temporal rhythm.

关 键 词：雷公藤甲素 心肌毒性 时间节律 

分 类 号：R285.5[医药卫生—中药学]