硫化氢复合浅低温对突触内N-甲基-D-天冬氨酸受体及其反应元件结合蛋白信号通路的影响

发布时间：2018-01-07 03:29

  本文关键词：硫化氢复合浅低温对突触内N-甲基-D-天冬氨酸受体及其反应元件结合蛋白信号通路的影响　出处：《医学研究生学报》2014年07期 　论文类型：期刊论文

  更多相关文章： 硫化氢 低温 N-甲基-D-天冬氨酸受体 环磷酸腺苷反应元件结合蛋白 脑缺血 再灌注损伤

【摘要】：目的研究表明硫化氢(H2S)能调节大脑N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptors,NMDARs)的功能,但其在脑复苏中的作用仍需进一步阐明。文中通过观察H2S复合浅低温对大鼠全脑缺血再灌注后海马NMDARs的亚单位NR2A、NR2B及其环磷酸腺苷反应元件结合蛋白(phospho-cAMP response element binding protein,p-CREB)信号通路的影响,旨在探讨H2S是否存在脑复苏作用及其发挥作用的潜在机制。方法雄性SD大鼠随机分为5组(n=20):假手术组、模型组、浅低温组、硫氢化钠(NaHS)组、浅低温+NaHS组。采用Pulsinelli-Brierley四血管阻塞法建立大鼠全脑缺血再灌注损伤模型,缺血15min再灌注即刻NaHS组和浅低温+NaHS组腹腔注射14μmol/kg NaHS,浅低温组和浅低温+NaHS组行体表降温至肛温32~33℃。6h后断头取海马,分别采用分光光度计法测H2S的含量,Western blot法测NR2A、NR2B以及p-CREB的表达,RT-PCR法测脑源性神经营养因子(brain derived neurotrophic factor,BDNF)mRNA的水平,每组分别取4只于再灌注72 h取脑组织行HE染色观察CA1区锥体细胞病理改变。结果 1与假手术组海马组织H2S含量(15.2±2.0)nmol/g相比,各组均升高(P0.05);与模型组的H2S含量(25.2±3.5)nmol/g相比,浅低温组(26.5±3.5)nmol/g略升高(P0.05),而NaHS组(37.5±4.0)nmol/g和浅低温+NaHS组(38.7±4.4)nmol/g显著升高(P0.05);2与假手术组相比,各组NR2A、NR2B的灰度值均增高(P0.05),且模型组和浅低温组NR2A/NR2B1,NaHS组和浅低温+NaHS组NR2A/NR2B1;3与模型组的p-CREB表达(0.55±0.06)相比,浅低温组(0.99±0.15)、NaHS组(1.05±0.12)、浅低温+NaHS组(1.02±0.15)显著升高(P0.05);与模型组的BDNF mRNA表达量(0.83±0.12)相比,浅低温组(1.11±0.13)、NaHS组(1.27±0.16)、浅低温+NaHS组(1.35±0.16)也显著升高(P0.05);4与模型组相比,浅低温组、NaHS组、浅低温+NaHS组CA1区锥体细胞损伤程度均明显减轻,尤以浅低温+NaHS组减轻最明显。结论硫化氢复合浅低温可能通过选择性作用于突触内的NMDARs,进而激活其下游促存活CREB信号通路,发挥脑复苏的作用。
[Abstract]:Objective to study showed that hydrogen sulfide (H2S) can regulate the brain N- methyl -D- aspartate receptor (N-methyl-D-aspartate, receptors, NMDARs) function, but its effect on brain resuscitation remain to be elucidated. In this paper, through the observation of H2S and mild hypothermia on Houhai horse NMDARs in rats with cerebral ischemia reperfusion subunit NR2A, NR2B and the cAMP response element binding protein (phospho-cAMP response element binding protein, p-CREB) signal pathway, to explore the potential mechanism of the existence of H2S effects and cerebral resuscitation. Methods male SD rats were randomly divided into 5 groups (n=20): sham operation group, model group, mild hypothermia group, hydrosulfide sodium (NaHS) group, mild hypothermia group +NaHS. Occlusion was established in rats with cerebral ischemia reperfusion injury model by four vessel Pulsinelli-Brierley, ischemia 15min reperfusion group and mild hypothermia +NaHS immediate NaHS group intraperitoneal injection 14渭mol/kg NaHS,娴呬綆娓╃粍鍜屾祬浣庢俯+NaHS缁勮�屼綋琛ㄩ檷娓╄嚦鑲涙福�

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