甘氨酸对高果糖饮食诱导的大鼠胰岛素抵抗及认知功能损害的影响

摘要

目的:探讨肠源性内毒素血症(IETM)在长期高果糖饮食诱导的大鼠胰岛素抵抗(IR)及认知功能损害中的作用,及甘氨酸对其的保护机制.方法:模型组大鼠以8%果糖水喂养,干预组给予8%果糖+1%甘氨酸水喂养.每月检测体重及收缩压.8个月后,检测血糖、血脂、糖耐量及血浆内毒素(LPS)变化;ELISA法检测血浆胰岛素、血浆及皮层促炎因子水平;计算胰岛素抵抗指数(HOMA-IR);Western blotting测定皮层胰岛素受体信号转导蛋白的表达;应用Morris水迷宫测试大鼠认知功能.结果:模型组在第3月～第6月体重增长明显,第3月后收缩压明显升高;甘氨酸在第4月和第6月显著降低模型组体重增长,第4～第6月降低收缩压的升高.甘氨酸部分改善模型组血脂和糖耐量异常,降低血浆LPS、血浆胰岛素、HOMA-IR、血浆和皮层促炎因子水平.此外,甘氨酸还明显改善模型组皮层胰岛素信号转导蛋白的异常表达及认知功能损害.结论:长期高果糖饮食诱导大鼠发生外周及中枢的IR,同时伴有IETM和轻度炎症;甘氨酸通过减轻IETM改善高果糖饮食诱导的IR和认知功能损害.%AIM: To investigate the role of intestinal endotoxemia ( IETM ) in insulin resistance ( IR ) and cognitive impairment, and to explore the protective mechanisms of glycine in rats with high - fructose diet. METHODS: The rats in model group were fed with 8% fructose water, and the rats in intervention group were fed with water containing 8% fructose and 1% glycine. The body weight and systolic pressure were measured monthly. After 8 months, plasma glucose, plasma lipids, glucose tolerance and plasma endotoxin ( LPS ) were detected. Plasma insulin, pro - inflammatory cytokines in plasma and cerebral cortex were determined by ELISA, and HO MA - IR was also calculated. The molecules of insulin signaling pathway in cerebral cortex were determined by Western blotting. The cognitive functions of the rats were tested by Morris water maze. RESULTS: The weight gain in model group was increased from the 3rd month to the 6th month, and systolic pressure was increased after the 3rd month as compared with control group. Glycine significantly reduced the weight gain in the 4th month and the 6th month, and significantly reduced the systolic pressure from the 4th month to the 6th month. Meanwhile, glycine partly attenuated dyslipidemia and glucose intolerance, and lowered the levels of plasma LPS, plasma insulin, HOMA - IR and pro - inflammatory cytokines in plasma and cortex. Furthermore, glycine attenuated the abnormal expression of insulin signaling proteins and cognitive impairment. CONCLUSION: Long - term fructose diet induces the rats to peripheral and neuronal IR, which accompanies IETM and low - grade inflammation. Glycine attenuates IR and cognitive impairment by lowering IETM.