痔血胶囊肝毒性药物因素分析  

Analysis on Drug Factors for Hepatotoxicity of Zhixue Capsule

作　　者：范琼尹 赵保胜 张晶璇 李品 贾旭 王停 FAN Qiong-yin;ZHAO Bao-sheng;ZHANG Jing-xuan;LI Pin;JIA Xu;WANG Ting(Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China)

机构地区：[1]北京中医药大学北京中医药研究院

出　　处：《中国实验方剂学杂志》2018年第1期150-157,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81773994,81274181,81374056)

摘　　要：目的：通过均匀设计法安排大鼠长期毒性拆方实验,比较痔血胶囊5种拆方对大鼠肝毒性的影响,寻找引起痔血胶囊肝毒性的药物因素。方法：Wistar大鼠,雌雄各半,随机分为正常组、痔血胶囊1-5号拆方组,灌胃给予相应的药物,连续给药30 d。末次给药后,取材测试大鼠血清的天门冬氨酸氨基转移酶（AST）,丙氨酸氨基转移酶（ALT）,碱性磷酸酶（ALP）,总胆红素（TBIL）,γ-谷氨酰转移酶（GGT）等指标情况,并同时观察各组大鼠肝脏色泽、质地、肿块等形态情况,摘取肝脏和脑,计算肝脏绝对质量、脏器系数;取肝脏最大叶同一部位肝组织,做苏木素-伊红（HE）染色后进行病理组织学检查。结果：与正常组比较,痔血胶囊各拆方组一般状况良好,血清生化学检测拆方5号组GGT显著升高（P〈0.01）,拆方3,4,5号组肝脏绝对质量、脏器系数明显升高（P〈0.05,P〈0.01）,肝脏组织病理学主要表现为肝小叶周边带肝细胞小泡型脂肪变性;根据肝脏脂变评分回归分析,白鲜皮可能为痔血胶囊肝毒性的主要药物因素。结论：建立一种新的中药安全性评价模式,发现潜在毒性中药,为今后完善中药安全性基础数据提供支撑,同时指导临床安全用药及中药新药研发。Objective： To explore the drug factors for hepatotoxicity of Zhixue capsule,the uniform design method was used by comparing five different Chinese medicine prescriptions in rats. Method： Wistar rats were randomly divided into blank control group and five Zhixue capsule groups. The rats were administrated with different drugs by gavage for 30 days. After the last drug administration,blood was collected from abdominal aorta,and serum was taken by centrifugation. Aspartate aminotransferase（ AST）,alanine aminotransferase（ ALT）,alkaline phosphatase（ ALP）,total bilirubin（ TBIL） and γ-glutamyltransferase（ GGT） in serum were detected to indicate the liver injury. The livers were taken for weighing and calculating absolute liver weight and organ coefficient. The largest liver lobe was stained with hematorylin-eosin（ HE）,and then pathological examination was performed under the microscope. Result： Compared with normal control group,general conditions of rats of Zhixue capsule groups were good,GGT of Zhixue capsule No. 5 was significantly increased（ P〈0. 01）,absolute liver weight and organ coefficient of Zhixue capsule groups No. 3,No. 4 and No. 5 were significantly increased（ P〈0. 05,P〈0. 01）,and Zhixue capsule ethanol extracts showed a clear hepatotoxicity,and histopathological observation showed small bubble type fatty degeneration surrounding hepatic lobule. According to the regression analysis of the indicators,cortex dictam may be the main drug factors for hepatotoxicity of Zhixue capsule.Conclusion： It is possible to improve the basic data for the safety of traditional Chinese medicine,guide the clinical safety medication,and improve the research and development of traditional Chinese medicine.

关 键 词：痔血胶囊 肝毒性 均匀设计 白鲜皮 药物因素 

分 类 号：R285.5[医药卫生—中药学]