苦参碱和氧化苦参碱致小鼠肝毒性比较  

Comparison of liver toxicity of matrine and oxymatrine in mice

作　　者：郭秋平 金若敏[2] 

机构地区：[1]广州医药研究总院有限公司药物非临床评价研究中心,广东广州510240 [2]上海中医药大学药物安全评价中心,上海201203

出　　处：《中国药理学与毒理学杂志》2016年第7期736-740,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点基础研究发展计划(2009CB522807);广州市生物产业重大专项(201300000053);广州市海珠区科技计划项目(2012-CG-01)~~

摘　　要：目的比较苦参碱和氧化苦参碱的肝毒性,探索其肝毒性机制。方法 ICR小鼠单次ig给予苦参碱200 mg·kg^(-1)或氧化苦参碱200 mg·kg^(-1),第15天计算小鼠死亡率;采用生化分析仪检测谷丙转氨酶(GPT)、谷草转氨酶(GOT)、碱性磷酸酶(ALP)和乳酸脱氢酶(LDH)含量;HE染色法检查肝组织病理变化;ELISA法检测肝组织匀浆液超氧化物歧化酶(SOD)和谷胱甘肽(GSH)含量;TUNEL染色法检测肝细胞凋亡率。结果苦参碱组小鼠死亡率为80%,氧化苦参碱组小鼠全部存活。与正常对照组相比,苦参碱组死亡小鼠血清酶GPT,GOT和ALP明显升高(P<0.05),氧化苦参碱组小鼠仅血清ALP升高(P<0.05);HE染色结果表明,苦参碱组8只死亡小鼠中4只小鼠肝细胞变性、灶性坏死(P<0.05),氧化苦参碱组10例中1只小鼠肝细胞轻度坏死;ELISA结果表明,苦参碱组死亡小鼠肝组织匀浆液SOD和GSH含量降低(P<0.05,P<0.01),氧化苦参碱组仅GSH含量降低(P<0.05);苦参碱组存活小鼠和氧化苦参碱组小鼠肝细胞凋亡率均升高(P<0.05)。结论苦参碱和氧化苦参碱对小鼠均具有肝毒性,苦参碱的肝毒性大于氧化苦参碱,肝毒性机制与氧化应激和诱导细胞凋亡有关。OBJECTIVE To compare the liver toxicity of matrine and oxymatrine,and to explore their toxic mechanism. METHODS Thirty ICR mice were randomly divided into normal control,matrine 200 mg·kg（-1）and oxymatrine 200 mg·kg（-1）groups,10 mice per group. After single ig administration of corresponding drugs or water,animal mortality was calculated at the 15 thday. The content of glutamic-pyruvic transaminase（GPT）,glutamic-oxalacetic transamin（GOT）,alkaline phosphatase（ALP）and lactate dehydrogenase（LDH）in serum were detected. Histopathological changes of the liver were examined by HE stain. The content of superoxide dismutase（SOD）and glutathione（GSH）in liver homogenates were detected by ELISA. Hepatocyte apoptosis was detected by Tunel stain. RESULTS The mortality rate of mice in two groups was 80% and 0,respectively. GPT,GOT and ALP contents of dead mice in matrine group were significantly higher than that in normal control group（P〈0.05）. In oxymatrine group,only the content of ALP was increased（P〈0.05）. Four of the eight dead mice in matrine group exhibited liver cell necrosis（P〈0.05）,while only 1/10 mice in oxymatrine group had a mild liver cell necrosis（P〈0.05）.The content of SOD and GSH of dead mice in matrine group was lower than that in control group（P〈0.05,P〈0.01）. The content of GSH in oxymatrine group was also decreased（P〈0.05）. The apoptosis rate of liver cells in dead mice in matrine group was increased（P〈0.05）. CONCLUSION A large dose of matrine and oxymatrine can produce liver toxicity. At an equal dosage,the liver toxicity of matrine is significantly higher than that of oxymatrine. The toxic mechanism is related to oxidative stress and apoptosis.

关 键 词：苦参碱 氧化苦参碱 肝毒性 

分 类 号：R285.1[医药卫生—中药学]