高脂饮食诱导胰岛素抵抗大鼠血浆游离脂肪酸与肿瘤坏死因子α的动态变化

Dynamic changes of free fatty acids and tumor necrosis factor-alpha concentration in high-fat-fed induced rat model of insulin resistance

目的:观察高脂饮食饲养下的大鼠血浆游离脂肪酸和肿瘤坏死因子α的浓度变化特点,分析其与胰岛素抵抗之间的关系。方法:实验于2005-03/04在解放军第四军医大学实验动物中心完成。选择健康清洁级雄性SD大鼠16只,以随机数字表法将大鼠分成2组,即对照组和高脂饮食组,各8只。①对照组给予普通饲料喂养(热量15kJ/g,脂肪占总热量12%)。②高脂饮食组给予高脂饲料喂养(热量22kJ/g,脂肪占总热量56%)。实验期间每天称取饲料消耗量,每7d空腹称大鼠质量及尾部取血1次。血浆胰岛素和肿瘤坏死因子α浓度以放免法测定,血浆葡萄糖以葡萄糖氧化酶法测定,胰岛素抵抗程度以HOMA模型胰岛素抵抗指数表示。结果:全部16只大鼠在实验过程中均无死亡,全部进入结果分析。①高脂饮食组HOMA-胰岛素抵抗指数21,28d与本组0d值比较明显升高(2.38±0.10,2.44±0.19,2.00±0.23,P<0.01),与对照组同期比较亦明显升高(2.02±0.18,2.06±0.11,P<0.01)。②高脂饮食组游离脂肪酸浓度21,28d与本组0d基础值比较明显升高[(0.62±0.05),(0.68±0.05),(0.55±0.05)mmol/L,P<0.05],与对照组同期比较亦明显升高[(0.54±0.06),(0.57±0.07)mmol/L,P<0.05];且游离脂肪酸水平与HOMA-胰岛素抵抗指数呈正相关关系(r=0.61,P<0.01)。③两组动物血浆肿瘤坏死因子α均无变化。结论:①游离脂肪酸的升高与胰岛素抵抗指数产生密切相关,结果数据尚难以分清因果关系。②高脂饮食喂养的大鼠胰岛素抵抗指数产生与血浆肿瘤坏死因子α的水平升高无关。

AIM： To observe the changing characteristics of plasma free fatty acids （FFA） and tumor necrosis factor （TNF）-α rats fed with high-fat diet, and analyze the relationship between FFA, TNF-α and insulin resistance. METHODS： The experiment was conducted in the Central Laboratory for Animals, Fourth Military Medical University of Chinese PLA from March to April 2005. Sixteen male SD rats of clean grade were selected and randomly divided into two groups： control group and high-fat diet group with 8 rats in each group. ①Rats in the control group were fed with standard diet （consisted of 12% fat, total 15 kJ/g）.②Rats in the high-fat diet group were fed with high-fat diet （consisted of 58% fat, total 22 kJ/g）. The food consumptions during the experiment were measured per day, and the body mass was measured weekly and blood samples were taken from rats by tail bleeding every 7 days. Levels of plasma insulin and TNF-α were determined with radio-immunochemical method. Plasma glucose was determined by glucose oxidase method. The insulin resistance was expressed by the insulin resistance index （IRI） of Homa-model analysis （HOMA-IR）. RESULTS： A total of 16 rats were involved in the analysis of results, no rat died in the experiment.①On the 21^th and 28^th day, the HOMA-IR of rats in the high-fat diet group were significantly increased than the Od value （2.38±0.10,2.44±0.19,2.00±0.23,P 〈 0.01）, and those were obviously increased than those in the control group at synchronization （2.02±0.18, 2.06±0.11 ,P 〈 0.01 ）. ②The plasma FFA concentrations on the 21^th and 28^th day in rats of the high-fat diet group remarkably increased more than the Od value of this group [（0.62±0.05）, （0.68±0.05）, （0.55±0.05） mmol./L, P 〈 0.05], while those significantly increased more than those in the control group at synehronization[（0.54±0.06）, （0.57±0.07） mmol/L,P 〈 0.05]. Moreover, the plasma FFA was positively correlated with HOMAIR （r=-0.61 ,P 〈 0.01）. ③There was no change of plasma TNF-α in rats of both groups. CONCLUSION： ①Increased FFA is closely associated with IRI, while the causation cannot be distinguished completely by data in the results.② The IRI of rats fed with high-fat diet is nor correlated with the increased level of TNF-α.