H_2S对缺血再灌注神经元的保护作用及机制  

The effect and mechanism of H_2S protecting neurons against ischemia-reperfusion injury

作　　者：邵建林[1] 万晓红[2] 王玲玲[1] 王俊科[1] 叶青山[1] 马宏仲[1] 

机构地区：[1]中国医科大学第一临床学院麻醉科 [2]昆明医学院第二附属医院SICU,昆明650101

出　　处：《中华神经医学杂志》2007年第6期545-549,共5页Chinese Journal of Neuromedicine

摘　　要：目的研究H2S对缺血再灌注损伤后神经元存活信号转导通路ERK1/2/P^(90RSK)的影响。方法将培养7 d的海马神经元随机分为5组:正常培养组(C组)、缺血再灌注组(I/R组)、缺血再灌注+NaHS组(NaHS组)、缺血再灌注+NaHS+U-0126(ERK抑制剂)组(U组)、缺血再灌注+NaHS+Rapamycin(RS6K抑制剂)组(R组)。C组神经元按正常培养方法培养。NaHS组神经元在神经元进行缺血再灌注时加入NaHS使其终浓度为150μmol/L。U组和R组在加入150μmol/L NaHS的同时分别加入U-0126 10μmol/L或Rapamycin lO nmol/L。各组行细胞存活力、神经元凋亡、cAMP、磷酸化ERK1/2(PERK1/2)和磷酸化P^(90RSK)(PP^(90RSK))蛋白表达的检测。结果NaHS显著增加了cAMP的浓度(与I/R组比较,P<0.01)、PERK1/2蛋白(与I/R组比较,P<0.05)和PP^(90RSK)蛋白(与I/R组比较,P<0.05)表达,同时增加了神经元存活率(与I/R组比较,P<0.05)、降低了神经元凋亡率(与I/R组比较,P<0.05);U-0126抑制了PERK1/2蛋白(与NaHS组比较,P<0.05)和PP^(90RSK)蛋白(与NaHS组比较,P<0.05)表达同时使神经元存活率降低(与NaHS组比较,P<0.05)、神经元凋亡率升高(与NaHS组比较,P<0.05);Rapamycin抑制了PP^(90RSK)蛋白(与NaHS组比较,P<0.05)表达同时使神经元存活率降低(与NaHS组比较,P<0.05)、神经元凋亡率升高(与NaHS组比较,P<0.05)而不影响PERK1/2的表达(与NaHS组比较,P>0.05)。结论H_2S通过cAMP激活了ERK1/2/P^(90RSK)信号通路,在海马神经元缺血再灌注时抑制了神经元的凋亡,保护了神经元。Objective To investigate the effect of hydrogen sulfide （H2S） on ERK1/2/P^90RSK signal transduction pathway of neuronal survival after ischemia-reperfusion injury. Methods The hippocampus neurons cultured for 7 d were randomly divided into five groups： normal culture group （group C）, ischemia-reperfusion group （group I/R）, ischemia-reperfusion ＋NariS group （group NariS）, ischemia-reperfusion＋NaHS＋U-0126 （ERK inhibitor） group （group U） and ischemia-reperfusion＋NaHS＋ Rapamycin （RS6K inhibitor） group （group R）. Neurons in group C were cultured by normal culturing method. In group NariS, when ischemia-reperfusion occurred to neurons, NariS was added to make their final concentration to be 150 μmol/L. In group U and group R, 150 μmol/L NariS was added together with 10 μmol/L U-0126 or 10 nmol/L Rapamycin simultaneously and respectively. Neuronal viability and apoptosis were measured; the level of cAMP and protein expressions of phosphorylated ERK1/2 （PERK1/2） and phosphorylated （p^90RSK） were detected. Results NariS evidently enhanced the concentration of cAMP （compared with group I/R, P〈0.05）, and protein expressions of PERK1/2 （compared with group I/R, P〈0.05） and P^90RSK （compared with group I/R, P〈0.05）; meanwhile, Narisincreased neuronal viability （compared with group I/R, P〈0.05） and decreased neuronal apoptosis （compared with group//R, P〈0.05）; U-0126 inhibited protein expressions of PERK1/2 （compared with group NariS, P〈0.05） and P^90RSK （compared with group NariS, P〈0.05）, increased neuronal apoptosis （compared with group NariS, P〈0.05） and decreased neuronal viability （compared with group NariS, P〈0.05）; Rapamycin inhibited the protein expression of P^90RSK （compared with group NariS, P〈0.05）, increased neuronal apoptosis （compared with group NariS, P〈0.05） and decreased neuronal viability （compared with group NariS, P〈0.05）, but it had no impact on the protein expression of PERK1/2

关 键 词：H2S ERK1/2 P^90RSK 细胞信号转导 神经元缺血再灌注 

分 类 号：R741[医药卫生—神经病学与精神病学]