肝郁脾虚胰岛素抵抗肥胖大鼠模型的建立与评价

Establishment and Evaluation Of A Rat Model Of Insulin Resistance And Obesity Induced By Liver Depression And Spleen Deficiency

目的:建立长期肝郁脾虚证大鼠肥胖和胰岛素抵抗模型。方法:用慢性束缚、塑料夹夹尾、慢性束缚+塑料夹夹尾3种方法诱导大鼠长期肝郁脾虚肥胖模型,筛选出最佳方法后再对该模型进行更全面的考察和评价。结果:3种造模方法诱导出的大鼠肝郁脾虚症状均较明显,摄食量和体质量早期均显著减少而后期均有所增加。尤其是束缚+夹尾组大鼠后期体质量增加较稳定,于第8周时与正常对照组比较差异有统计学意义。进一步对束缚+夹尾法诱导的模型评价结果可见,体质量在第8周时超过正常对照组,血糖具有缓慢上升的趋势,TG升高,HDL降低,肝脏和肾脏指数增加,脾脏和胸腺则出现萎缩,血浆胰岛素、胰高血糖素和皮质酮水平增加,而葡萄糖输注率则降低。结论:长期慢性束缚加夹尾法能成功诱导肝郁脾虚证大鼠肥胖和胰岛素抵抗,这种方法具有成模后肝郁脾虚症状明显、体质量增加较稳定,伴有血脂代谢和激素分泌的异常,同时出现胰岛素抵抗和免疫抑制现象,与人类因情志不遂导致的肝郁脾虚证相似。

Objective： This article focused on establishment and evaluation of the best method for inducing rat model of insulin resistance and obesity with the syndrome of liver stagnation and spleen deficiency. Methods： Experimental insulin resistance and obesity rat models were induced by chronic constraint, clamp of tails, or both chronic constraint and clamp of tails respectively. The syndrome of liver stagnation and spleen deficiency and body weight were determined to select the best method for inducing obesity rats model. According to the purpose of the experiment, insulin resistance and obesity rat models with syndrome of liver stagnation and spleen deficiency were induced by both chronic constraint and clamp of tails. The insulin resistance and obesity rat model was systematically evaluated in body weight, plasma glucose, plasma lipids, weights of internal organs, as well as insulin and its counter-regulatory hormone levels（glucagons and corticosterone）. Results： It was found that the syndrome of liver stagnation and spleen deficiency could be induced by chronic constraint, clamp of tails, or both chronic constraint and clamp of tails. Only the obesity model induced by both chronic constraint and clamp of tails was stable. The evaluations of this method were as follows： body weight decreased at first, but increased later; plasma lipids were observed with the changes of high TG level and low HDL level; the weights index of liver and kidney were increased and that of spleen and thymus decreased; insulin level and corticosterone level increased significantly; glucagons level increased a little; glucose infusion rate（GIR） decreased significantly. Conclusion： The insulin resistance and obesity rat model with syndrome of liver stagnation and spleen deficiency was successfully induced by both chronic constraint and clamp of tails in rats. The characteristic of this model was as follows： stable body weight increase; maintainance of immune deficiency; changes of plasma lipids and hormone levels were similar to that of liver stagnation and spleen deficiency syndrome in human beings.