血管紧张素Ⅳ对糖尿病大鼠认识功能及其受体表达变化的影响.docVIP

血管紧张素Ⅳ对糖尿病大鼠认识功能和其受体表达变化的影响 李 娟 肖 谦 张栋珉 （重庆医科大学附属第一医院老年科内分泌组 重庆 400016） 【摘要】目的：观察血管紧张素Ⅳ（AngⅣ）对糖尿病大鼠认知功能、AT4受体表达的影响。方法：40只SD雄性大鼠随机分成正常对照组、糖尿病组、糖尿病+ AngⅣ组，建立STZ糖尿病大鼠模型，成模后第12周，Morris水迷宫测试其学习记忆能力，测试结束后对糖尿病+ AngⅣ组进行侧脑室注射，糖尿病组注射等体积生理盐水，持续1周，再进行Morris水迷宫测试，免疫组化观察AT4受体的表达，RT-PCR检测AT4受体mRNA表达水平变化。结果：AngⅣ组和糖尿病组比较，Morris水迷宫测试中潜伏期明显缩短（P＜0.05），通过平台位置次数增加（P＜0.05），AT4受体蛋白及其mRNA表达下降（P＜0.05）。结论：AngⅣ对糖尿病大鼠认知功能有保护作用，AT4受体表达下调可能是其作用机制之一。 【关键词】AngⅣ；糖尿病；认知功能；AT4受体 Effect of AngiotensinⅣon cognition function of diabetic rat and the expression of its receptor AT4 【Abstract】Objective：To explore the effect of AngiotensinⅣ(AngⅣ) on cognition function of diabetic rat and the expression of its receptor AT4. Methods：40 SD male rats were divided into the normal group, diabetic model group, AngⅣ treatment group randomly. Streptozotocin-diabetic rat model was established, 12 weeks after model was established, the learning and memory abilities of rats were tested with the Morris water maze. Then, AngⅣ was injected into the lateral ventricle of AngⅣ treatment group rats, once a day lasted for a week，normal sodium was injected into diabetic model group rats for a week . The learning and memory abilities of rats were tested with the Morris water maze again. The mRNA and protein level of AT4 in hippocampus were detected by RT-PCR and immunohistochemical method. Result：Compared with diabetic model group, the AngⅣ treatment group showed a significant decrease in the mean time of escape latencies（P＜0.05）,and a increase in the number of passing the original platform position（P＜0.05）.And expression of AT4 receptor protein and mRNA in hippocampus were decreased significantly（P＜0.05）.Conclusion：It is conclude that AngⅣ could improve cognitive ability in diabetic rat，perhaps the expression of AT4 receptor decrease maybe one of the mechanism of it. 【Key words】AngⅣ； Diabetes；Cognition；AT4 receptor 糖尿病中枢神经系统的并发症包括代谢、神经化学、形态学、电生理及神经行为学等方面的改变，其主要临床表现为认知功能障碍。肾素－血管紧张素系统（RAS）在全身广泛分布，中枢独立的RAS除对血压调节有重要作用之外，还参与脑部其它功能的调