海马Ghrelin对大鼠学习记忆的影响及机制研究

Effects and mechanisms of Ghrelin on learning and memory in hippocampus of rats

目的探讨海马Ghrelin对大鼠学习记忆能力的影响及机制。方法采用海马CAl区微量注射Ghrelin及一氧化氮合酶（NOS）抑制剂等，利用跳台实验及Morris水迷宫进行定位航行实验和空间搜索实验，观察海马Ghrelin对大鼠学习记忆的影响并分析可能机制。结果海马CA1区注射Ghrelin可明显增加大鼠学习记忆能力，表现为跳台实验中大鼠从安全台跳下的潜伏期明显延长[（5．3±1．7）minVS（3．5±1．6）min，t=2．44，P〈0．05]，5min内大鼠遭受电击次数明显减少[（0．8±0．7）次VS（1．9±1．0）次，t=2．85，P〈0．05]，Morris水迷宫实验中大鼠找到平台的潜伏期明显缩短[（10．6±3．6）minVS（17．2±6．1）min，t=2．95，P〈0，01]，但海马CA1区注射Ghrelin受体阻断剂[D—Lys（3）]-GHRP-6可明显消除上述Ghrelin促进大鼠学习记忆的作用[潜伏期（3．5±1．7）minVS（4．9±1．2）min，t=2．13，P〈0．05]；注射NOS抑制剂L—NAME可明显减弱Ghrelin促进大鼠学习记忆能力[潜伏期（3．4±1．5）minVS（4．9±1．2）min，t=2．47，P〈0．05]；而海马CA1区注射Ghrelin抗血清可明显减弱大鼠认知作用，表现为跳台实验中大鼠从安全台跳下的潜伏期明显缩短[（1．8±1．4）minVS（3．5±1．6）min，t=2．53，P〈0．05]，5rain内大鼠遭受电击次数明显增加[（3．2±0．9）次VS（1．9±1．0）次，t=3．06，P〈0．01]，Morris水迷宫实验中大鼠找到平台的潜伏期明显延长[（25．8±7．0）rainVS（17．2±6．1）rain，t=2．93，P〈0．01]。结论海马CA1区内外源性Ghrelin均可提高大鼠学习记忆能力，而该作用可能与海马内NO合成有关。

Objective To explore the effects and mechanisms of Ghrelin of hippocampus on the learning and memory in rats. Methods Step-down test and morris water maze were used to test the effects of learning and memory ability by means of microinjecting Ghrelin, Ghrelin receptor blocker [ D-Lys（3） ] -GHRP-6, L-NAME or Ghrelin antibody into hippecampal CA1 area in rats. Results Ghrelin injection of hippecampal CA1 area could promoter learning and memory ability in rats. It showed that the escaped latent period was significantly lengthened （5.3 ± 1.7 vs 3.5 ± 1.6, t = 2.44, P 〈 0.05 ） and the wrong numbers in 5 rain were obviously decreased in escape response test（0.8 ± 0.7 vs 1.9 ± 1.0, t = 2.85, P 〈 0.05 ） ; and the latency of looking for the plat was significantly shorter in morris water maze test （ 10.6 ± 3.6 vs 17.2 ± 6.1, t = 2.95, P 〈 0.01 ）. However the effects above- mentioned on learning and memory was eliminate after Ghrelin receptor blocker [ D-Lys（3 ） ]-GHRP-6 injection of hippocampal CA1 area（3.5 ± 1.7 vs 4.9 ± 1.2, t= 2.13, P〈 0.05 ）. Moreover L-NAME could significantly weak the effect of Ghrelin on promoting learning and memory in rats（ 3.4 ± 1.5 vs 4.9 ± 1.2, t = 2.47, P〈 0.05 ）. Ghrelin antibody injection of hippocampal CA1 area could significantly decrease learning and memory ability in rats, it showed that the escaped latent peroid was markedly shortened （ 1.8 ± 1.4 vs 3.5 ± 1.6, t = 2.53, P〈 0.05 ） and the wrong numbers in 5rain were obviously increased （3.2 ±0.9 vs 1.9 ± 1.0, t = 3.06, P 〈 0.01 ） in escape response test. The latency of looking for the plat was significantly lengthened in morris water maze （ 25.8 ±7.0 vs 17, 2 ± 6.1, t = 2.93, P 〈 0.01 ）. Conclusion Both endogenous and exogenous Ghrelin could elevate the learning and memory ability in hippocampus, and the effects may be related to the synthesis of NO in hippocampus.