大鼠急性肝损伤(肝郁脾虚证)病证结合模型的研究  

Research on rat models of acute liver injury with syndrome of liver depression and spleen deficiency

作　　者：黄娜娜[1,2] 孙晓倩[2] 杨倩[3] 李晓宇[1] 孙蓉[1] 

机构地区：[1]山东省中医药研究院,山东济南250014 [2]山东中医药大学,山东济南250355 [3]日照市中医医院,山东日照276800

出　　处：《中国中药杂志》2016年第23期4400-4407,共8页China Journal of Chinese Materia Medica

基　　金：国家"重大新药创制"科技重大专项(2009ZX09502-015);山东省自主创新和成果转化项目(2014ZZCX02104);国家自然科学基金面上项目(81374059);泰山学者工程专项(Ns201511107)

摘　　要：建立适宜于抗急性肝损伤(肝郁脾虚证)中药复方活性发现、药效评价和新药研发的方证相应动物模型。依照中医病因病机演变规律和现代病理机制研究,抽提适宜于急性肝损伤(肝郁脾虚证)大鼠动物模型评价的证候、确定积分,根据药证相符原则选定逍遥丸和水飞蓟宾葡甲胺片为模型反证药物,大鼠每天腹腔注射猪血清,并按分组给予不同配比高脂低蛋白饲料及食用乙醇进行诱导;共7 d。实验期间每日观察大鼠的体重、食量、饮水量及一般观察并对其进行中医证候积分,实验结束检测大鼠血清ALT,AST,PA,TBIL,TBA等肝功能指标的水平,检查肝组织病理学变化。在造模1周后,各模型组的大鼠均达到明显急性肝损伤程度,且大鼠主证、次证均符合肝郁脾虚证的证候表现。与正常对照组比较,血清ALT和AST活性升高,TBIL和TBA含量升高,PA含量降低;肝组织病理形态学检查显示各模型组的大鼠均出现炎细胞浸润、嗜酸性变或嗜酸性脂肪变,反证药物组可不同程度改善上述病变表现。腹腔注射猪血清+高脂低蛋白饲料(89.5%玉米粉、10%猪油、0.5%胆固醇)+10%食用乙醇连续造模7 d,经药物反证,可建立拟临床肝郁脾虚证的急性肝损伤大鼠模型,具有成模耗时短、死亡率低、动物状态与临床患者证候表现相近等特点,可适用于抗急性肝损伤(肝郁脾虚证)中药复方活性发现、药效评价、新药研发和临床方证相关性研究与机制探讨。This paper aimed to establish animal models which are suitable for the activity found,efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism. Xiaoyao pill and silibin meglumine tablets were used as drug counter evidence for models in accordence with the principle of consistence of prescription and syndrome. Rats model were fed with high-lipid and low-protein fodder of different proportion and induced by intraperitoneal injection with pig serum,intragastric administration with edible alcohol once a day for7 days. Daily record of body weight,daily food intake and daily water intake were conducted day after day in experimental session. Symptoms were also observed and evaluated by score at the same time. The contents of ALT,AST,PA,TBIL and TBA in serum were detected and histopathological changes of liver were checked at the ending of experiment. Obvious acute liver injury occurred to all rats in model groups at 1 week following model induction. Both main symptoms and secondary symptoms were consistent with syndrome manifestation of liver depression and spleen deficiency. Compared with normal control group,the activity of ALT,AST and contents of TBIL,TBA in serum increased and the content of PA decreased. Liver tissue pathological morphology showed inflammatory cells infiltration,eosinophilic or eosinophilic adipose change in hepatocytes of rats in model groups. All the above lesions manifestation could be improved by drug counterevidence. By the disproof of medicine,rat models of acute liver injury with syndrome of liver depression and spleen deficiency could be induced by fed with high-l

关 键 词：急性肝损伤 肝郁脾虚证 病证结合 大鼠 动物模型 

分 类 号：R-332[医药卫生] R285.5