本文關鍵詞：硫化氫復合淺低溫對突觸內(nèi)N-甲基-D-天冬氨酸受體及其反應元件結合蛋白信號通路的影響　出處：《醫(yī)學研究生學報》2014年07期 　論文類型：期刊論文

  更多相關文章： 硫化氫 低溫 N-甲基-D-天冬氨酸受體 環(huán)磷酸腺苷反應元件結合蛋白 腦缺血 再灌注損傷

【摘要】：目的研究表明硫化氫(H2S)能調節(jié)大腦N-甲基-D-天冬氨酸受體(N-methyl-D-aspartate receptors,NMDARs)的功能,但其在腦復蘇中的作用仍需進一步闡明。文中通過觀察H2S復合淺低溫對大鼠全腦缺血再灌注后海馬NMDARs的亞單位NR2A、NR2B及其環(huán)磷酸腺苷反應元件結合蛋白(phospho-cAMP response element binding protein,p-CREB)信號通路的影響,旨在探討H2S是否存在腦復蘇作用及其發(fā)揮作用的潛在機制。方法雄性SD大鼠隨機分為5組(n=20):假手術組、模型組、淺低溫組、硫氫化鈉(NaHS)組、淺低溫+NaHS組。采用Pulsinelli-Brierley四血管阻塞法建立大鼠全腦缺血再灌注損傷模型,缺血15min再灌注即刻NaHS組和淺低溫+NaHS組腹腔注射14μmol/kg NaHS,淺低溫組和淺低溫+NaHS組行體表降溫至肛溫32~33℃。6h后斷頭取海馬,分別采用分光光度計法測H2S的含量,Western blot法測NR2A、NR2B以及p-CREB的表達,RT-PCR法測腦源性神經(jīng)營養(yǎng)因子(brain derived neurotrophic factor,BDNF)mRNA的水平,每組分別取4只于再灌注72 h取腦組織行HE染色觀察CA1區(qū)錐體細胞病理改變。結果 1與假手術組海馬組織H2S含量(15.2±2.0)nmol/g相比,各組均升高(P0.05);與模型組的H2S含量(25.2±3.5)nmol/g相比,淺低溫組(26.5±3.5)nmol/g略升高(P0.05),而NaHS組(37.5±4.0)nmol/g和淺低溫+NaHS組(38.7±4.4)nmol/g顯著升高(P0.05);2與假手術組相比,各組NR2A、NR2B的灰度值均增高(P0.05),且模型組和淺低溫組NR2A/NR2B1,NaHS組和淺低溫+NaHS組NR2A/NR2B1;3與模型組的p-CREB表達(0.55±0.06)相比,淺低溫組(0.99±0.15)、NaHS組(1.05±0.12)、淺低溫+NaHS組(1.02±0.15)顯著升高(P0.05);與模型組的BDNF mRNA表達量(0.83±0.12)相比,淺低溫組(1.11±0.13)、NaHS組(1.27±0.16)、淺低溫+NaHS組(1.35±0.16)也顯著升高(P0.05);4與模型組相比,淺低溫組、NaHS組、淺低溫+NaHS組CA1區(qū)錐體細胞損傷程度均明顯減輕,尤以淺低溫+NaHS組減輕最明顯。結論硫化氫復合淺低溫可能通過選擇性作用于突觸內(nèi)的NMDARs,進而激活其下游促存活CREB信號通路,發(fā)揮腦復蘇的作用。
[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,嫻呬綆娓╃粍鍜屾祬浣庢俯+NaHS緇勮浣撹〃闄嶆俯鑷寵倹娓，

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