大鼠脂肪肝肝郁脾虚证的模型  

Rat Models of Fatty Liver Due to Liver Depression and Spleen Deficiency

作　　者：孙晓倩[1,2] 孙蓉[1] SUN Xiao-qian SUN Rong(Shandong Academy of Chinese Medicine, Ji＇nan 250014, China Shandong University of Traditional Chinese Medicine, Ji＇nan 250355, China)

机构地区：[1]山东省中医药研究院,济南250014 [2]山东中医药大学,济南250355

出　　处：《中国实验方剂学杂志》2017年第10期92-98,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家"重大新药创制"科技重大专项(2009ZX09502-015);国家自然科学基金面上项目(81374059);山东省自主创新和成果转化项目(2014ZZCX02104);泰山学者工程专项经费项目(ts201511107)

摘　　要：目的:建立适宜于抗脂肪肝肝郁脾虚证中药复方活性发现、药效评价、新药研发及中医方-证对应的病证结合动物模型。方法:根据中医病因病机的演变规律和现代临床病理机制的研究,建立适宜于脂肪肝肝郁脾虚证模型评价的证候积分表,并选择联苯双酯滴丸和三七脂肝丸作为模型反证药物,模型组大鼠每天按分组给予不同配比的高脂低蛋白饲料和不同浓度的乙醇,每周2次腹腔注射猪血清,联苯双酯滴丸组按8.1 mg·kg^(-1)给药,三七脂肝丸组按2.7 g·kg^(-1)给药,连续给药14 d。实验期间,观察大鼠的一般情况、体重、日食量、日水量,并进行中医证候积分,实验结束后,检测大鼠血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),γ-谷氨酰转肽酶(γ-GT),总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)的含量,并对肝组织进行病理学检查。结果:与正常组比较,模型组大鼠的体重、日食量、日饮水量增加缓慢,指标ALT,AST,γ-GT,TC,TG,LDL-C水平显著升高,HDL-C水平降低,病理学检查可见脂肪肝大鼠肝脏脂肪变性、脂肪粒,且行为学观察发现,大鼠出现的主证、次证均符合肝郁脾虚证的证候表现,表明3个模型组均造模成功,其中,模型1组有3只大鼠死亡,模型2组有1只大鼠死亡。反证药物组可不同程度改善上述病变表现。结论:脂肪肝肝郁脾虚证动物模型具有死亡率低、耗时短,可用于抗脂肪肝(肝郁脾虚证)中药复方活性发现、药效评价和临床方证相关性研究与机制探讨。Objective： To establish animal models of fatty liver due to liver depression and spleen deficiency that were suitable for activity discovery of traditional Chinese medicine（TCM） compounds,efficacy evaluation,new drug research and development and correspondence between formula and syndrome of TCM.Method： A syndrome scoring table that was suitable for evaluating the rat models was established according to the evolution laws of etiology and pathogenesis of TCM and the modern clinical pathological mechanism. At the same time,bifendate pills and Sanqi Zhigan pills were selected as drug counterevidence for the models. Rats in model groups were given different proportions of high-fat and low-protein fodder and different concentrations of alcohol every day,and intraperitoneally injected with pig serum twice a week. Drug groups were given with respectively bifendate pills and Sanqi Zhigan pills（8. 1 mg·kg-1,2. 7 g·kg-1） for 14 consecutive days. General status,weight,daily appetite and water quantity of the animals were observed during the experiment,and TCM syndromes were scored. The levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,γ-glutamine transpeptidase（γ-GT）,total cholesterol（TC）,triglycerides（TG）,low density lipoprotein-cholesterol（LDL-C）,and high density lipoprotein-cholesterol（HDL-C） in serum were detected. And the pathological changes of liver tissue were observed after the experiment. Result： Compared with normal group,body weight,daily food and water intake of rats increased slowly in model group,and the contents of ALT,AST,γ-GT,TC,TG and LDL-C increased significantly, while the level of HDL-C decreased. Pathological examination showed that fatty degeneration and fat granule were observed in hepatocytes of rats in model group. Behavioral observation found that main syndromes and minor symptoms of rats in model group conformed to the syndrome manifestation of liver depression and spleen deficiency,which suggested that the three model groups w

关 键 词：脂肪肝 肝郁脾虚证 动物模型 毒性 

分 类 号：R285.5[医药卫生—中药学]