胰岛素对糖尿病认知功能障碍大鼠海马InsR表达的影响

Effect of insulin on InsR expression in rats with diabetic cognitive impairment

关键词:  糖尿病认知功能障碍  胰岛素受体  胰岛素

Key words:  [Key words]　diabetes cognitive impairment  insulin receptor  insulin

摘要:

[摘要]　目的　检测海马胰岛素受体（insulin receptor, InsR）表达的变化，探讨InsR的表达对糖尿病大鼠认知功能的影响以及胰岛素的干预效果。　方法　成年健康雄性SD（Sprague-Dawley）大鼠36只，随机分为3组：糖尿病组（12只）、胰岛素干预组（12只）及对照组（12只），每组再均分为1、3个月组。应用单次腹腔注射链脲佐菌素（Streptozotocin，STZ）的方法制作糖尿病模型。对照组给予单次腹腔注射柠檬酸-柠檬酸钠缓冲液，血糖正常。所有大鼠每周2个固定时间点测血糖。胰岛素干预组大鼠每日皮下注射2~3 U低精蛋白锌胰岛素，根据血糖情况调整用量，保证空腹血糖处于正常范围。于1、3个月分批行Morris水迷宫实验评估认知功能水平后处死，取脑、切片，行免疫组织化学染色，观察各组大鼠海马InsR表达的变化。　结果　糖尿病1个月组大鼠，逃避潜伏期延长，脑内InsR表达减少，与对照组比较，差异均有显著性意义（P<0.05）。糖尿病3个月组大鼠，逃避潜伏期延长明显，海马InsR表达减少明显，与糖尿病1个月组比较，差异均有显著性意义（P<0.05）。胰岛素干预1个月组，与对照组比较，逃避潜伏期略延长，海马InsR表达减少，差异均无显著性意义；与糖尿病1个月组比较，逃避潜伏期缩短，海马InsR表达增加，差异均有显著性意义（P<0.05）。胰岛素干预3个月组与干预1个月组比较，逃避潜伏期延长，海马InsR表达减少明显，差异均有显著性意义（P<0.05）；与糖尿病3个月组比较，逃避潜伏期、InsR表达差异均无明显。　结论　InsR表达减少是糖尿病认知功能障碍的原因之一；早期应用胰岛素干预可以延缓认知功能损害，具体机制需进一步探讨。

Abstract:

[Abstract] Objective　To observe the change of congnitive function and the expression level of hippocampal insulin receptors (InsR) in 1 month and 3 months of diabetic rats, explore the effect of InsR on diabetic rats and investigate that whether insulin can be applied to prevent diabetic cognitive impairment.　Methods　36 healthy adult male SD (Sprague-Dawley) rats, weight 180-240 g, were divided into 3 groups randomly: diabetic group (n=12), insulin treatment group (n=12) and control group (n=12), and then each group was divided into 2 groups equal in amount randomly: 1 month group and 3 months group. Diabetic group and insulin treatment group rats were induced by streptozotocin injection. Fixed time to measure blood glucose of all rats twice a week. Insulin treatment group rats were injected insulin daily, and we adjusted insulin dosage according to the blood glucose level to ensure blood glucose in normal range. All the rats underwent the test of Morris water maze in 1 month and 3 months. After the assessment on cognitive function of the 1 month and 3 months rats that experienced the Morris water maze experiment, the expression of InsR in brain were observed.　Results　Compared with the control group, 1 month group of diabetic rats appeared cognitive impairment and their expression of InsR reduced, which has statistical difference (P<0.05). Compared with 1 month diabetic group, the cognitive impairment of 3 months diabetic group was obviously aggravated and their expression of InsR reduced more significantly, which has statistical difference as well (P<0.05). 1 month group of insulin treatment rats with no significant cognitive impairment, and their expression of InsR reduced slightly. Compared with the control group, there are no difference. Compared with the 1 month diabetic group, which has statistical difference (P<0.05). 3 months group of insulin treatment rats appeared cognitive impairment and their expression of InsR reduced obviously. Compared with control group, which has statistical difference (P<0.05). Compared with 1 month group of insulin treatment rats,which has statistical difference as well (P<0.05). Compared with 3 months group of diabetic rats, there are no statistical difference.　Conclusion　Diabetic cognitive impairment is closely related to InsR, the reduced InsR expression may contribute to diabetic cognitive impairment. Early intervention of insulin has protective effect on the brain,then delay cognitive impairment. However, as the extension of the duration, the insulin treatment group rats still show cognitive impairment, which suggests that long-term application of insulin can not prevent the occurrence of cognitive impairment. Mechanisms need to be further explored.