大鼠脂肪肝肝郁脾虚证的模型

发布时间：2019-05-13 12:37

【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。
[Abstract]:Objective: to establish an animal model suitable for the activity discovery, efficacy evaluation, new drug research and development of traditional Chinese medicine (TCM) prescription and syndrome for anti-fatty liver, liver depression and spleen deficiency syndrome. Methods: according to the evolution of etiology and pathogenesis of traditional Chinese medicine and the study of modern clinicopathological mechanism, the syndrome integral table suitable for evaluating the model of liver depression and spleen deficiency syndrome of fatty liver was established, and biphenylene diester dropping pills and Panax notoginseng zigan pills were selected as model counter-syndrome drugs. The rats in the model group were given different ratios of high fat and low protein diet and different concentrations of ethanol every day, and the pig serum was injected intraperitoneally twice a week, and the biphenylene diester dropping pill group was given 8.1 mg kg~ (- 1). Sanqi Zhigan pill group was given 2.7g kg~ (- 1) continuously for 14 days. During the experiment, the general condition, body weight, daily food volume, daily water quantity and TCM syndrome score were observed. At the end of the experiment, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), was detected. The contents of (TC), (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in 纬-GT), total cholesterol (TC),) and liver tissue were examined. Results: compared with the normal group, the body weight, daily food volume and daily drinking water of the model group increased slowly, the level of ALT,AST, 纬-GT,TC,TG,LDL-C increased significantly, and the level of HDL-C decreased. Pathological examination showed fatty liver steatosis and fatty granule in rats, and behavioral observation showed that the main and secondary syndromes of the rats were in accordance with the syndrome of liver depression and spleen deficiency, indicating that all the three model groups were successful in the establishment of the model, among which the main syndrome and the secondary syndrome were consistent with the syndrome of liver depression and spleen deficiency. Three rats died in model 1 and one in model 2. The anti-syndrome drug group can improve the above pathological changes to varying degrees. Conclusion: the animal model of fatty liver with liver depression and spleen deficiency syndrome has the advantages of low mortality and short time, which can be used to find the activity of traditional Chinese medicine against fatty liver (liver depression and spleen deficiency syndrome), and to study the correlation and mechanism of clinical prescription and syndrome.
【作者单位】：山东省中医药研究院;山东中医药大学;
【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)
【分类号】：R285.5;R-332

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