【作者】 张涛；

【导师】 刘源；

【作者基本信息】 中国人民解放军军事医学科学院 ， 预防兽医学， 2009， 硕士

【摘要】 目的国内外流行病学调查和实验研究已证实,高脂饮食是诱发胰岛素抵抗综合征(IRS)的重要环境因素,但不同脂肪在IRS发生过程中所起的作用可能不同。本实验拟通过给予大鼠相同脂肪含量、不同脂肪的饮食,分析猪油、豆油、氢化椰子油、乳脂4种不同脂肪的高脂日粮对大鼠血液生化指标动态变化趋势、胰岛素敏感性、脏器损伤、脂联素血清含量及其在脂肪组织中mRNA表达水平的影响。方法40只雄性SD大鼠随机分为5组,其中对照组给予普通日粮,4个高脂组分别给予脂肪热量比相同的猪油、豆油、氢化椰子油、乳脂高脂日粮。喂养6周,每两周测定空腹血糖、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、总胆固醇(TC)、胰岛素,根据胰岛素敏感性指数(ISI)=㏑ 1/( FPG×FINS)评定大鼠的胰岛素敏感性,6周后取肝脏、胰腺、心脏做切片,观察肝脏、胰岛、冠状动脉的损伤情况,并取肾周脂肪测定脂联素mRNA的表达。结果1.高脂组平均日饲料消耗量以氢化椰子油组最多、猪油组最少,实验末,乳脂组大鼠体重最高、猪油组最低;2.各组血糖均呈上升趋势,但变化情况不同,第15天时豆油组测定值显著低于对照组(P﹤0.05);3.整个实验过程中高脂组血清TG均低于对照组,第15天时氢化椰子油组测定值显著低于对照组(P﹤0.05),实验末,乳脂组显著高于其它高脂组(P﹤0.05);4.高脂组血清HDL-c均呈下降趋势,从15天开始高脂组均显著低于对照组(P﹤0.05)并以豆油组下降幅度最大;5.各高脂组血清胰岛素呈上升趋势,但变化情况不同,而对照组呈下降趋势,实验末,猪油组、乳脂组、豆油组均显著高于对照组(P﹤0.05);6.各实验组ISI均呈下降趋势,但高脂组下降更快,29天时乳脂组已经显著低于对照组(P﹤0.05),实验末,猪油组、乳脂组均显著低于对照组(P﹤0.05);7.整个实验过程中各组间血清总胆固醇没有明显差异;8.高脂组均出现肝细胞灶性坏死、局部炎细胞浸润、较多的空泡,但各组间无明显损伤差异;而各实验组均未发现胰岛、心脏冠状动脉的组织结构损伤;9.高脂组血清脂联素含量均下降,并以乳脂组下降最大,豆油组下降最小,但与对照组无明显差异(P>0.05),其中氢化椰子油组血清脂联素与HDL-c、TG、TC呈正相关性,相关系数分别为(r=0.784,p=0.021;r=0.768,p=0.026;r=0.949,p=0.0003),猪油组血清脂联素与血糖、体重呈负相关性,相关系数分别为(r=-0.742,p=0.035;r=-0.721,p=0.044);10.高脂组肾周脂肪组织脂联素mRNA表达水平与对照组无明显差异。结论1.四种高脂日粮诱发IRS大鼠模型的综合效果依次为乳脂、猪油、豆油、氢化椰子油;2.高乳脂摄入导致大鼠最高的血清甘油三酯、血糖及体重;3.高猪油摄入导致大鼠最高的血清胰岛素水平,最低的胰岛素敏感性,但该组能量摄入量最少、体重最低,该组的血清脂联素与血糖、体重呈负相关性;4.高豆油摄入导致大鼠最低的血清HDL-c、血糖,短期内能刺激胰岛素显著上升而后又下降;5.高氢化椰子油摄入,短期内能刺激TG显著下降而后又上升,该组的血清脂联素与HDL-c、TG、TC呈正相关性;6.高脂饮食在短时间内不会引起大鼠空腹血糖、血清总胆固醇显著升高;7.高脂饮食首先对大鼠肝脏造成损伤,表现为肝细胞灶性坏死、局部炎细胞浸润、出现较多的空泡,但短期内对胰岛和冠状动脉无明显损伤;8.高脂饮食导致大鼠血清脂联素含量降低,但短时间内对大鼠肾周脂肪组织脂联素mRNA表达水平没有影响。更多还原

【Abstract】 Objective Previous studies have indicated that the development of insulin resistance syndrome(IRS) were closely related to high-fat diets.The particular type and source of dietary fat, however, may have its own impact on the characters of IRS.Rats were fed a series of high-fat diets, identical but for fat source: lard,bean oil,hydrogenated-coconut oil and butterfat. The influence of different diets on rats’blood biochemical parameters, insulin sensitivity index, hepatic、panceatic island、coronary artery scathe, adiponectin content in plasma and its mRNA express in adipose tissue were analyzed, which can provid reference for establishment and empirical study of this animal model.Methods Forty 7-weeks-old healthy male SD rats assigned at random into five groups. The normal group was fed on standard laboratory chow(10.97% of calories as fat) and experimental groups were fed on isocaloric high fat diets(46.15% of calories as fat)for 6 weeks.Serum glucose(GLU), triglyeride(TG), HDL-cholesterol, cholesterol (CHO) and insulin were measured fortnightly interval. The insulin sensitivity was estimated by ISI index,ISI =㏑ 1/(FPG×FINS). At the end of the experiment, hepatic、panceatic island and coronary artery pathological examination was observed, moreover, the adiponectin mRNA expression was tested by RT-PCR.Results1. Hydrogenated-coconut oil group consumed the most chow,while lard group consumed the least; at the end, butterfat group were the heaviest of all groups, but lard group were the lightest;2. The glucose level of all groups increased, but there was no obvious different among the five groups. The bean oil group had considerably lower glucose level compared with normal group on the 15th day(P﹤0.05);3. Serum TG was significantly increased in butterfat group compared with other high-fat groups(P﹤0.05)in the end;4. High-fat feeding groups exhibited obviously lower HDL-cholestero(lP﹤0.05) than normal group, especially the bean oil group;5. Serum insulin increased in High-fat feeding groups,but normal group decreased. Moreover, it was significantly high in Lard、butterfat and bean oil groups compared with normal group(P﹤0.05)in the end;6. As for ISI, butterfat group had been lower than normal group(P﹤0.05)since the 29th day, in addition, butterfat and lard groups were both lower than normal group(P﹤0.05)in the end; 7. However there were mild difference in TC among the five groups;8. Hepatic was impaired in High-fat feeding groups including focalne necrosis, inflammatory cell infiltration and much vacuole; however,pancreatic islet and coronary artery were not impaired;9. High-fat feeding groups exhibited lower adiponectin level than normal group especially the butterfat group;in Hydrogenated-coconut oil group,seruma adiponectin content was positively related to HDL-c(r=0.784,p=0.021)、TG (r=0.768,p=0.026)and TC(r=0.949,p=0.0003),while in Lard group it was negatively related to glucose(r=-0.742,p=0.035) and weigh(tr=-0.721,p=0.044);10. There was no significant different in the adiponectin mRNA expression between high-fat feeding groups and normal group.Conclusion1. High butterfat chows had the best effect of the four high fat feeds on establishment of IRS rat model, and lard was better than bean oil, but hydrogenated-coconut oil was the worst;2. High butterfat chows had the greatest sustained effect on TG , weight gain and glucose level;3. High Lard chows appears to produce the greatest level of serum insulin, the lowest ISI, but this group has the lowest energy intake and weight, moreover seruma adiponectin level was negatively related to glucose and weight;4. High Bean oil chows had the greatest effect on HDL-c and glucose, it could induce serum insulin significantly increased but decreased latter;5. High Hydrogenated-coconut oil chows could induce serum insulin significantly decresed but increased latter, and seruma adiponectin level was positively related to HDL-c、TG and TC;6. High-fat feeding did not induce fasting serum glucose and cholesterol of rat increased in 6 weeks;7. Hepatic was impaired by high-fat feeding for 6 weeks; however,pancreatic islet and coronary artery were not impaired;8. Serum adiponectin content decreased in rat fed with high-fat diet, but the mRNA expression level of adiponectin did not decrease .更多还原