狼毒醋制前后对小鼠肠道毒性及结肠水通道蛋白表达的影响  

Effects of toxic fractions of Euphorbiae Ebracteolatae Radix on toxicity of mice intestinal tract and colon aquaporins expression level before and after vinegar processing

作　　者：刘莲 郁红礼[1,2,3] 王奎龙[1] 吴皓[1,2,3] 王卫[1] 张元斌 于生[1] 尹厚庆 LIU Lian;YU Hong-li;WANG Kui-long;WU Hao;WANG Wei;ZHANG Yuan-bin;YU Sheng;YIN Hou-qing(Pharmacology College of Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory of Chinese Medicine Processing,Nanjing 210023,China;Engineering Center of State Ministry of Education.for Standardization of Chinese Medicine Processing,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药炮制重点实验室,江苏南京210023 [3]国家教育部中药炮制规范化及标准化工程研究中心,江苏南京210023

出　　处：《中国中药杂志》2018年第12期2516-2521,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(81202915);江苏省自然科学基金面上项目(BK20171493)

摘　　要：为研究狼毒炮制前后毒性变化规律,以氯仿为提取溶剂,富集狼毒二萜类成分毒性部位,并将氯仿提取后药渣以95%乙醇及水依次提取,得非氯仿部位;并以相同方法提取狼毒醋制后的氯仿提取部位。小鼠灌胃给药,以粪便含水量、十二指肠及结肠含水量及小鼠结肠组织的水通道蛋白AQP1,AQP3,AQP4蛋白表达水平为指标,考察氯仿提取部位与非氯仿部位,及醋制前后狼毒的肠道毒性变化。研究结果显示,狼毒氯仿毒性部位可导致小鼠粪便及十二指肠、结肠肠道含水量显著升高,并导致结肠AQP1蛋白表达水平显著降低,AQP3,AQP4蛋白表达水平显著增高,且氯仿部位的肠道毒性作用显著高于非氯仿部位;醋制后粪便含水量、十二指肠及结肠含水量均显著下降,结肠中AQPs蛋白表达趋向正常。结果表明狼毒氯仿毒性部位可导致小鼠腹泻、肠道水肿,其肠道毒性作用与其干扰结肠中水通道蛋白的表达、促使肠道水液转运失常相关;醋制能够降低狼毒的肠道毒性,表明中药传统醋制法炮制狼毒的科学性。To investigate the toxicity changes of Euphorbiae Ebracteolatae Radix（ EER） before and after vinegar processing,toxic diterpenoids were concentrated with chloroform as extraction solvent from EER. Then the residue was extracted for non-chloroform extract with 95% ethanol and water after extraction with chloroform. The chloroform extraction of vinegar processed EER was prepared with the same method. The mice received the drug by oral administration. Moisture content in mice feces,duodenum and colon tissue,aquaporin AQP1,AQP3,AQP4 protein expression levels were assayed as the indexes to investigate the toxicity variation of chloroform fraction,non-chloroform fraction,as well as intestinal tract toxicity before and after vinegar processing of EER. The results showed that the chloroform fraction extracted from EER could significantly increase the moisture content in mice feces,duodenum and colon,and decrease AQP1 protein expression level,increase AQP3 and AQP4 protein expression levels in the colon. The intestinal toxicity of the chloroform extract was significantly higher than that of non-chloroform extract. The moisture content in mice feces,duodenum and colon was significantly decreased,and the AQPs protein expression tended to be normal in the colon after vinegar processing. The results showed that the chloroform fraction extracted from EER could lead to diarrhea,intestinal edema,and the intestinal toxicity action was associated with interfering AQPs protein expression and promoting intestinal fluid transport disorder in mice. Vinegar-processing could reduce intestinal toxicity of EER,so vinegar processing was considered to be the scientific processing method of EER.

关 键 词：狼毒 醋制法 肠道毒性 水通道蛋白 醋制减毒 

分 类 号：R285.5[医药卫生—中药学]