Ghrelin和Obestatin对大鼠空间学习记忆能力影响

【摘要】  目的 探讨Ghrelin和Obestatin对正常大鼠空间学习记忆能力的影响。方法 大鼠随机分为Ghrelin高剂量组、低剂量组和对照组?1;Obestatin高剂量组、低剂量组和对照组?2。Ghrelin各组双侧海马CA3区微量注射不同剂量Ghrelin和等量生理盐水;Obestatin各组侧脑室微量注射不同剂量的Obestatin和等量生理盐水。应用水迷宫方法检测大鼠的空间学习记忆能力。结果 水迷宫隐匿平台实验中Ghrelin高剂量组的潜伏期与对照组?1相比明显缩短，撤平台实验中Ghrelin高剂量组在原象限游泳的时间和总路程的百分比与对照组相比明显增加。Obestatin各组在隐匿平台和撤平台实验中的结果都没有统计学差异。结论 海马微量注射Ghrelin可明显提高大鼠的空间学习记忆能力，该作用可能与Ghrelin激活海马部位有关;侧脑室注射Obestatin, 在水迷宫实验中未能观察到大鼠空间学习记忆能力的提高。 
【关键词】  Ghrelin;Obestatin;学习;记忆;海马;大鼠
[ABSTRACT] Objective To explore the effects of Ghrelin and Obestatin on the ability of learning and memory in rats. Methods Rats were randomly divided into six groups as: high?dose Ghrelin (HDG), low?dose Ghrelin (LDG) and control?1; high?dose Obestatin (HDO), low?dose Obestatin (LDO) and control?2. Different doses of Ghrelin and same amount of normal saline were given by micro?injection into the hippocampus CA3 in Ghrelin group; Different doses of Obestatin and same amount of normal saline were given by lateral cerebroventricular injection (icv). The ability of learning and memory was tested by Morris water maze. Results The latency of swimming time and distance in the HDG were decreased significantly compared with that in the control group. In the probe test, the rats in HDG stayed longer time and swimming distance in the origin quadrant were longer than that of the control group. The results showed no difference between Obestatin groups and control group in the hiding platform test and probe test. Conclusion Micro?injection of Ghrelin into the hippocampus has an effect of improving the ability of learning and memory in rats, whereas icv injection of Obestatin has no such effect.
　　[KEY WORDS] Ghrelin; Obestatin; Learning; Memory; Hippocampus; Rats
　　Ghrelin是1999年KOJIMA等[1]发现的生长素促分泌素受体1a(GHS?R1a)的内源性配体。大量实验表明，Ghrelin具有很强的刺激生长激素释放、促进摄食、减少脂肪分解等作用[2]。由于Ghrelin在机体饥饿状态下主要由胃黏膜泌酸腺A细胞分泌，因此大量实验集中于Ghrelin对摄食的启动作用和能量平衡的调节作用的研究。最近的研究结果表明，脑室和外周给予Ghrelin具有促进正常大鼠学习记忆的能力[3,4]。Obestatin与Ghrein是来源于同一个基因的肽类激素，对它的报道目前有许多争议。ZHANG等[5]指出，大鼠腹腔和脑室内注射Obestatin均可以抑制摄食。但是有研究表明，Ghrelin可借助特殊的转运系统通过血?脑脊液屏障，而Obestatin却不能通过该屏障，并且它在血液中很快地被降解[6]。HOLST等[7]甚至认为，Obestatin并非GPR39的配体。GOURCEROL等[8]报道，腹腔内注射Obestatin (30、100、300 mg/kg)并不影响累积摄食量。关于Obestatin对学习记忆能力的影响，VALERIA等[9]通过跳台实验和十字迷宫实验证实，Obestatin有增强记忆和促焦虑的作用。本实验采用双侧海马CA3区微量注射Ghrelin、侧脑室微量注射Obestatin，用水迷宫的方法观察其对大鼠空间学习记忆能力的影响。
　　1 材料与方法