长期高脂饮食对大鼠海马胰岛素受体底物的基因表达及其学习和记忆能力的影响

摘要

目的 探讨长期高脂饮食对大鼠海马胰岛素受体底物的基因表达及大鼠空间学习和记忆能力的影响.方法100只4周龄雄性SD大鼠,随机分为普通饮食组(CD,n=40)、高脂饮食组(HFD,n=60),CD组给予普通饮食、HFD组给予高脂饮食,分别在4、8、12、16周,20周末于两组中随机选择8只大鼠进行Morrise水迷宫测试,连续5 d测试结束后处死大鼠,取血清检测代谢参数,取海马CA1区检测胰岛素受体底物-1(IRS-1)和胰岛素受体底物-2(IRS-2)的基因表达量.结果 与CD组相比,HFD组大鼠的逃避潜伏期和游泳距离长,平均游泳速度快,停留在平台所在象限时间短;血清胰岛素含量升高,海马CA1区IRS-1和IRS-2的基因表达量下调(P<0.05).结论 长期高脂饮食导致肥胖大鼠胰岛素抵抗,干扰了海马的胰岛素受体底物的基因表达,影响脑内胰岛素代谢,损害其空间学习和记忆等认知功能,加速认知退化.%Objective To assess the effect of long-term high-fat diet on the expressions of insulin receptor substrates in the hippocampus and spatial learning and memory ability of obese rats. Methods A total of 100 4-week-old male SD rats were randomly divided into two groups and fed with common diet (CD group, n=40) or high-fat diet (HFD group, n=60) for 16 weeks. At 4, 8, 12, 16 and 20 weeks, 8 rats were randomly selected from each group for testing their spatial learning and memory function using Morris water maze. After the tests, the rats were sacrificed for measurement of the metabolic parameters and detection of the expressions of insulin receptor substrate-1(IRS-1)and IRS-2 mRNAs in the CA1 region of the hippocampus.Results Compared with those in CD group, the rats in HFD group showed a prolonged escape latency,longer swimming distance, faster average swimming speed, and shorter stay in the platformat 12 weeks. In HFD group, the serum levels of total cholesterol,triglyceride,low-density lipoprotein cholesterol,and fasting insulin were all significantly increased (P<0.05)and the level of high-density lipoprotein cholesterol decreased(P<0.01)in comparison with those in CD group at each of the time points. No significant difference was found in fast glucose levels between the two groups (P>0.05), but the expressions of IRS-1 and IRS-2 mRNAs were significantly decreased in HFD group at 12 weeks(P<0.05).Conclusion In obese rats,long-term feeding with high-fat diet leads to insulin resistance,which interferes with hippocampal expression of insulin receptor substrates and insulin metabolism to cause impairment of the cognitive function and accelerate cognitive deterioration.