Zhang Mengling, Sun Xiangrong, Guo Feifei, Gong Yanling, Xu Luo
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 May;28(5):455-9.
To observe the protective effect of ghrelin on hippocampal injury induced by global cerebral ischemia/reperfusion (I/R) and explore its effect mechanisms.
The male Sprague-Dawley (SD) rats were randomly divided into four groups,namely sham group, I/R group,normal saline (NS)+I/R group and Ghrelin+I/R group, with 42 rats in each group. The model of I/R was reproduced by clipping bilateral carotid artery of rats 15 minutes and then releasing them for 60 minutes. There were no challenges for rats in sham group,just exposed their carotid artery.Ghrelin+I/R group and NS+I/R group were challenged by injecting 1 μ.L ghrelin or NS into lateral ventricle before I/R. Some of brain tissue in the rats was harvested after experiment to determine the levels of malonaldehyele (MDA),myeloperoxidase (MPO) and glutathione (GSH) in hippocampus by using chemical colorimetry and observe infarct sizes and histopathology. Single extracellular neuron discharge in other rats was recorded to observe the activity of glutamic sensitive neurons (Glu-N) and γ-aminobutyric acid (GABA) sensitive neurons (GABA-N) in hippocampus CA1 region of rats suffered I/R.
Compared with sham group, the levels of MDA and MPO in hippocampus of rats in the I/R group were raised markedly, the level of GSH was decreased significantly, the infarct sizes was increased significantly and pycnosis neurons were increased markedly. All sorts of indexes between NS+I/R group and I/R group showed no significantly statistical significance.Compared with NS+I/R group,the levels of MDA and MPO in hippocampus of rats in the Ghrelin+I/R group were decreased significantly [MDA (nmol/g): 16.4 ± 4.2 vs.24.5 ± 6.7,MPO (nmol/g):6.4 ± 1.8 vs.10.2 ± 2.9,both P ＜ 0.05],the activity of GSH was risen remarkably (μmol/g:2.65 ± 0.72 vs.1.66 ± 0.50,P ＜ 0.05),the infarct sizes of hippocampus were reduced markedly [(43.9 ± 9.5)％ vs.(77.0 ± 12.7)％,P ＜ 0.01],the number of pycnosis neuron was reduced markedly (cells:36.2±4.5 vs.47.1 ±6.1,P ＜ 0.01).The results of electrophysiology showed that the discharge frequency of Glu-N and GABA-N in hippocampus CA1 region of rats in I/R group increased markedly as compared with sham group, and no significant difference in the discharge frequency of Glu-N and GABA-N between NS+I/R group and I/R group. Compared with NS+I/R group, injected ghrelin could make the discharge frequency of Glu-N in hippocampus CA1 region of rats decreased markedly (Hz:3.81 ±0.67 vs.4.98±0.33 at ischemia,3.01 ±0.37 vs.3.77 ± 0.41 at reperfusion, both P ＜ 0.05),and the discharge frequency of GABA-N increased markedly (Hz:5.62 ± 0.54 vs.3.62±0.39 at ischemia,4.81±0.48 vs.3.71±0.21 at reperfusion, both P ＜ 0.05)..
Ghrelin might protect hippocampal neuron after I/R iniury, and neuron excitability decrease might be related
观察胃饥饿素对全脑缺血/再灌注（I/R）诱导的海马损伤的保护作用，并探讨其作用机制。
将雄性Sprague-Dawley（SD）大鼠随机分为四组，即假手术组、I/R组、生理盐水（NS）+I/R组和胃饥饿素+I/R组，每组42只。通过夹闭大鼠双侧颈动脉15分钟然后再松开60分钟来复制I/R模型。假手术组大鼠不进行夹闭操作，仅暴露其颈动脉。胃饥饿素+I/R组和NS+I/R组在I/R前通过向侧脑室注射1μL胃饥饿素或NS进行干预。实验结束后取部分大鼠脑组织，采用化学比色法测定海马中丙二醛（MDA）、髓过氧化物酶（MPO）和谷胱甘肽（GSH）水平，并观察梗死灶大小和组织病理学变化。记录其他大鼠的单细胞外神经元放电情况，以观察I/R大鼠海马CA1区谷氨酸敏感神经元（Glu-N）和γ-氨基丁酸（GABA）敏感神经元（GABA-N）的活性。
与假手术组相比，I/R组大鼠海马中MDA和MPO水平显著升高，GSH水平显著降低，梗死灶大小显著增加，固缩神经元显著增多。NS+I/R组与I/R组之间的各项指标均无显著统计学差异。与NS+I/R组相比，胃饥饿素+I/R组大鼠海马中MDA和MPO水平显著降低[MDA（nmol/g）：16.4±4.2 vs.24.5±6.7，MPO（nmol/g）：6.4±1.8 vs.10.2±2.9，均P＜0.05]，GSH活性显著升高（μmol/g：2.65±0.72 vs.1.66±0.50，P＜0.05），海马梗死灶大小显著减小[（43.9±9.5）％ vs.（77.0±12.7）％，P＜0.01]，固缩神经元数量显著减少（细胞数：36.2±4.5 vs.47.1±6.1，P＜0.01）。电生理结果显示，与假手术组相比，I/R组大鼠海马CA1区Glu-N和GABA-N的放电频率显著增加，NS+I/R组与I/R组之间Glu-N和GABA-N的放电频率无显著差异。与NS+I/R组相比，注射胃饥饿素可使I/R大鼠海马CA1区Glu-N的放电频率显著降低（缺血时Hz：3.81±0.67 vs.4.98±0.33，再灌注时Hz：3.01±0.37 vs.3.77±0.41，均P＜0.05），GABA-N的放电频率显著增加（缺血时Hz：5.62±0.54 vs.3.62±0.39，再灌注时Hz：4.81±0.48 vs.3.71±0.21，均P＜0.05）。
胃饥饿素可能对I/R损伤后的海马神经元具有保护作用，神经元兴奋性降低可能与之有关
