H_2S在大鼠心肺复苏后脑水肿中的作用及其对海马区巢蛋白表达的影响
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摘要
目的：探讨H2S在心肺复苏后脑损伤中的作用。
方法：取SD雄性大鼠45只,随机分为假手术(A)组、CPR(B)组和NaHS处理(C)组,A组5只,B组、C组按自主循环恢复(restoration of spontaneous circulation,ROSC)后6h、12h、24h、72h四个时间点各分四个亚组,每亚组各5只,每组共20只。参照经典窒息法制作心脏骤停模型。A组仅行置管及插管,B组制作心肺复苏模型大鼠,C组在B组基础上于CPR前一分钟静脉推注NaHS 10umol/kg(将称取的NaHS立即溶于0.5m1生理盐水中)。采用全自动酶标仪测定大鼠脑皮质H2S含量；721分光光度计测脑组织EB含量；免疫组化计Nestin阳性细胞数；测脑组织干/湿重比并采用原子吸收光谱法测脑组织钠、钾离子含量,行NDS评分。
结果：(1)脑组织H2S含量变化：与A组相比,B组6h、12h脑组织H2S含量增加(6h,p<0.05,12h,p<0.01),24h下降(p<0.05),72 h恢复A组水平(p>0.05)。与B组同时间点比,C组中各时间点脑组织H2S含量增加(p<0.05)。(2)脑水肿指标变化：与A组相比,B组脑组织含水量、EB含量、钠离子含量随时间点逐渐上升,至24h达到高峰,72h呈下降趋势。钾离子含量逐渐下降,24h至低谷,72h呈上升趋势,与B组同时间点比,C组6h、12h、24 h EB含量下降(p<0.05),C组12h、24 h、72 h脑组织含水量及脑组织钠离子含量下降,钾离子含量上升(p<0.05)。(3)脑组织巢蛋白、NDS评分变化：与A组相比,B组巢蛋白、NDS评分表达升高,且其值随时间点逐渐增加(p值均<0.01),与B组同时间点比,C组各时间点巢蛋白表达、NDS评分增加(p值均<0.05)。行相关性分析显示：脑组织含水量与脑组织钠离子含量变化呈正相关(r=0.688,p<0.01),与脑组织钾离子含量呈负相关(r=-0.554,p<0.05)；与脑组织EB含量相关(r=0.854,p<0.01),将H2S与脑组织含水量进行相关性分析,结果显示B组中,H2S与脑组织含水量不相关,C组H2S与脑组织含水量呈负相关(r=-0.663,p<0.05)。
结论：小剂量外源性H2S可通过降低大鼠脑组织钠离子含量,增加钾离子含量,减轻BBB通透性的增加而降低CPR后脑组织含水量,同时还可上调脑组织巢蛋白的表达,改善NDS评分；H2S可能通过上述机制影响心肺复苏后脑损伤的发生发展。
Objective:To investigate the role of H2S in the formation of brain edema and the effect of H2S on the expression of nestin in hippocampus after CPR.
Methods:Forty-five male Sprague-Dawley(SD) rats were randomly diveded into normal group(group A), model group(group B) and NaHS pretreatment group(group C). There were 5 rats in sham-operated group,20 rats in model group and NaHS pretreatment group,20rats were separately divided into four subgroups at 6h、12h、24h、72h after ROSC with 5 rats in each subgroup.The cardiac arrest model of rat was established according to asphyxy method. Catheters were inserted into left femoral artery and vein of rats while tracheal intubation was performed in A group, the cardiac arrest model of rat was established in rats of group B and C,0.5ml NaHS solution (lOumol/kg NaHS dissolving in physiological saline by the rat weight) was administered intravenously 1 minute before CPR. The level of H2S in cortex in brain tissue of rats in three groups were determined by universal Microplate Reader, the content of EB were measured by 721 spectrophotometer. immunohistochemistry method was adopted to calculate the amount of Nestin positive cells, the ratio of wet to BWC was calculated, atomic absorption spectrometry was adopted to measure the content of Na+and K+, NDS score was calculated.
Results:(1) Change of the level of H2S in brain tissue:Compared with group A, the level of H2S in brain tissue increased at 6h、12h、(6h、p<0.05,12h、p<0.01), and decreased at 24h (p<0.05),assumed a dynamic chang of rising and descending, returning to group A level at 72h (p>0.05). Compared with group B, the level of H2S in all time points of group C increased (p<0.05) in brain tissue. (2) Change of indicator in celebral edema:Compared with group A, the content of water, EB and Na+ of brain tissue increased gradually, peaked at 24h and assumed a trend of decreasing at 72h, the content of K+ of brain tissue decreased gradually, lowered at 24h and assumed a trend of increasing at 72h, Compared with crresponding time point of group B, the content of EB was decreased at 6h、12h、24 h in C group (p<0.05),the content of water and Na +decreased while the content of K+increased at 12h、24 h、72h in C group (p<0.05). (3)Change of the expression of nestin and NDS score:Compared with group A, the expression of nestin and NDS score increased in B group (p<0.01) and its data increased gradually with time points. Compared with crresponding time point of group B, the expression of nestin and NDS score increased in all subgroups of group C (p<0.05), Correlation analyse demonstrated that the content of water of brain tissue was positively correlated with the content of Na+ of brain tissue (r=0.688, p<0.01), negatively correlated with the content of K+ of brain tissue (r=-0.686, p<0.01), and was positively correlated with the content of EB of brain tissue (r=0.854,p<0.01);the level of H2S wasn't correlated with brain edema in group B, and was positively correlated with brain edema in group C (r=-0.663,p<0.01)
Conclusion:low level of exdogenous Hydrogen sulphide can decrease brain water content by decreasing the content of Na+ in brain tissue、increasing the content of K+ in brain tissue and mitigating BBB Permeability, while upregulate the expression of nestin in brain tissue,and thus increase NDS score. H2S may influence in the formation and progression of celebral injury after CPR though the above mechanism,
方法：取SD雄性大鼠45只,随机分为假手术(A)组、CPR(B)组和NaHS处理(C)组,A组5只,B组、C组按自主循环恢复(restoration of spontaneous circulation,ROSC)后6h、12h、24h、72h四个时间点各分四个亚组,每亚组各5只,每组共20只。参照经典窒息法制作心脏骤停模型。A组仅行置管及插管,B组制作心肺复苏模型大鼠,C组在B组基础上于CPR前一分钟静脉推注NaHS 10umol/kg(将称取的NaHS立即溶于0.5m1生理盐水中)。采用全自动酶标仪测定大鼠脑皮质H2S含量；721分光光度计测脑组织EB含量；免疫组化计Nestin阳性细胞数；测脑组织干/湿重比并采用原子吸收光谱法测脑组织钠、钾离子含量,行NDS评分。
结果：(1)脑组织H2S含量变化：与A组相比,B组6h、12h脑组织H2S含量增加(6h,p<0.05,12h,p<0.01),24h下降(p<0.05),72 h恢复A组水平(p>0.05)。与B组同时间点比,C组中各时间点脑组织H2S含量增加(p<0.05)。(2)脑水肿指标变化：与A组相比,B组脑组织含水量、EB含量、钠离子含量随时间点逐渐上升,至24h达到高峰,72h呈下降趋势。钾离子含量逐渐下降,24h至低谷,72h呈上升趋势,与B组同时间点比,C组6h、12h、24 h EB含量下降(p<0.05),C组12h、24 h、72 h脑组织含水量及脑组织钠离子含量下降,钾离子含量上升(p<0.05)。(3)脑组织巢蛋白、NDS评分变化：与A组相比,B组巢蛋白、NDS评分表达升高,且其值随时间点逐渐增加(p值均<0.01),与B组同时间点比,C组各时间点巢蛋白表达、NDS评分增加(p值均<0.05)。行相关性分析显示：脑组织含水量与脑组织钠离子含量变化呈正相关(r=0.688,p<0.01),与脑组织钾离子含量呈负相关(r=-0.554,p<0.05)；与脑组织EB含量相关(r=0.854,p<0.01),将H2S与脑组织含水量进行相关性分析,结果显示B组中,H2S与脑组织含水量不相关,C组H2S与脑组织含水量呈负相关(r=-0.663,p<0.05)。
结论：小剂量外源性H2S可通过降低大鼠脑组织钠离子含量,增加钾离子含量,减轻BBB通透性的增加而降低CPR后脑组织含水量,同时还可上调脑组织巢蛋白的表达,改善NDS评分；H2S可能通过上述机制影响心肺复苏后脑损伤的发生发展。
Objective:To investigate the role of H2S in the formation of brain edema and the effect of H2S on the expression of nestin in hippocampus after CPR.
Methods:Forty-five male Sprague-Dawley(SD) rats were randomly diveded into normal group(group A), model group(group B) and NaHS pretreatment group(group C). There were 5 rats in sham-operated group,20 rats in model group and NaHS pretreatment group,20rats were separately divided into four subgroups at 6h、12h、24h、72h after ROSC with 5 rats in each subgroup.The cardiac arrest model of rat was established according to asphyxy method. Catheters were inserted into left femoral artery and vein of rats while tracheal intubation was performed in A group, the cardiac arrest model of rat was established in rats of group B and C,0.5ml NaHS solution (lOumol/kg NaHS dissolving in physiological saline by the rat weight) was administered intravenously 1 minute before CPR. The level of H2S in cortex in brain tissue of rats in three groups were determined by universal Microplate Reader, the content of EB were measured by 721 spectrophotometer. immunohistochemistry method was adopted to calculate the amount of Nestin positive cells, the ratio of wet to BWC was calculated, atomic absorption spectrometry was adopted to measure the content of Na+and K+, NDS score was calculated.
Results:(1) Change of the level of H2S in brain tissue:Compared with group A, the level of H2S in brain tissue increased at 6h、12h、(6h、p<0.05,12h、p<0.01), and decreased at 24h (p<0.05),assumed a dynamic chang of rising and descending, returning to group A level at 72h (p>0.05). Compared with group B, the level of H2S in all time points of group C increased (p<0.05) in brain tissue. (2) Change of indicator in celebral edema:Compared with group A, the content of water, EB and Na+ of brain tissue increased gradually, peaked at 24h and assumed a trend of decreasing at 72h, the content of K+ of brain tissue decreased gradually, lowered at 24h and assumed a trend of increasing at 72h, Compared with crresponding time point of group B, the content of EB was decreased at 6h、12h、24 h in C group (p<0.05),the content of water and Na +decreased while the content of K+increased at 12h、24 h、72h in C group (p<0.05). (3)Change of the expression of nestin and NDS score:Compared with group A, the expression of nestin and NDS score increased in B group (p<0.01) and its data increased gradually with time points. Compared with crresponding time point of group B, the expression of nestin and NDS score increased in all subgroups of group C (p<0.05), Correlation analyse demonstrated that the content of water of brain tissue was positively correlated with the content of Na+ of brain tissue (r=0.688, p<0.01), negatively correlated with the content of K+ of brain tissue (r=-0.686, p<0.01), and was positively correlated with the content of EB of brain tissue (r=0.854,p<0.01);the level of H2S wasn't correlated with brain edema in group B, and was positively correlated with brain edema in group C (r=-0.663,p<0.01)
Conclusion:low level of exdogenous Hydrogen sulphide can decrease brain water content by decreasing the content of Na+ in brain tissue、increasing the content of K+ in brain tissue and mitigating BBB Permeability, while upregulate the expression of nestin in brain tissue,and thus increase NDS score. H2S may influence in the formation and progression of celebral injury after CPR though the above mechanism,
引文
[1]陶珍,陆兵勋,张运周,等.葡萄糖-磷酸酶多克隆抗体对大鼠血管源性脑水肿的治疗作用[J],南方医科大学学报,2006,26(7)：1041-1044.
[2]Chad K, Nicholson,JohnW.Calvert.Hydrogen sulfide and ischemia-reperfusion injury[J]. Pharmacol Res,2010,62(4):289-297.
[3]Lee M, Schwab C, Yu S,et al. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide[J]. Neurobiol Aging,2009,30 (10):1523-1534.
[4]Kimura Y,Kimura H.Hydrogen sulfide protects neurons from oxidative stress[J]. FASEB,2004,18(10):1165-1167.
[5]Tyagi N,Givvimani S, Qipshidze N,et al.Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice[J].Neurochem Int,2010,56(2):301-307.
[6]Tay AS, Hu LF, Lu M, et al. Hydrogen sulifde protects neuroues against hypoxicinjury via stimulation of ATP-senstive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway [J].Neuroscience,2010,167(2):277-286.
[7]Ren CL, Du AL, Li DL,et al. Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats[J].Brain Research,2010,12345:197-205.
[8]Minamishima S,Bougaki M,Sips PY.etal.Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice[J].circulation,2009,120(10):888-896.
[9]Papapetropoulos A, Pyriochou A, Altaany Z, etal.Hydrogen sulfide is an endogenous stimulator of angiogenesis[J]. PNAS,2009,106(51):21972-21977.
[10]Xiao F,Zhang S,Arnold TC,et al. Mild hypothemfia induced before cardiac arrest reduces brain edema formation in rats[J].Acad Emerg Med,2002,9(2):105-114.
[11]郭梅凤,刘励军,徐信发,等.大鼠心肺复苏后脑组织含水量和水通道蛋白-4的动态变化及相关性研究[J].中国急救医学,2006,26(9)：673-674.
[12]王姗姗,陈寿权,李章平,等。乌司他丁对心肺复苏后大鼠脑水肿和血脑屏障的作用[J],中华急诊医学杂志,2006,15(4)：338-341.
[13]Geocadin RG, Ghodadra R, Kimura T,et al. A novel quantitative EEG injury measure of global cerebral ischemia. Clin Neurophysiol,2000,111 (10):1779-1787
[14]Von Planta I,Weil MH,Von Planta M,et al.Cardiopulmonary resuscitation in the rat[J].J Appl Physiol,1988,65(6):2641-2647.
[15]Hans HL, Hendrickx, Rao GR, et al. Asphyxia cardiac arrest and resuscitation [J].Chin J Emery Med,2002,12(2):97-116.
[16]陈寿权,李章平,王姗姗,等.窒息法致大鼠心脏骤停模型复苏的影响因素[J].中华急诊医学[J],2005,14(10)：814-817.
[17]孟庆义,马勇,钱远宇,等.氨茶碱和肾上腺素对大鼠心脏停搏的作用[J].中华急诊医学,2005,14(6)：482-484.
[18]Hendrickx HHL, Rao GR, Safar P, et al. Asphyxia cardiac arrest and resuscitation in rats[J].Resuscitation,1984,12(2):97-116.
[19]American Heart Association.Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research[J]. Circulation,1996,94:232-233.
[20]Schneider A, Bottiger BW, Popp E. Cerebral Resuscitation After Cardiocirculatory Arrest[J].AnesthAnalg,2009,108(3):971-979.
[21]Shibuya N,Tanaka M,Yoshida M,et al.3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J].Antioxid Redox signal 2009, 11(4):703-714.
[22]Wang R.Twos conpany,threes acrowd:can H2S be the third endogenous transmitter? [J].FASEB,2002,16(13):1792-1798.
[23]Eto K, Asada T, Arima K, Makifuchi T, Brain hydrogen sulfide is severely decreased in Alzheimer's disease[J].Biochem Biophys Res Commun,2002 24;293(5):1485-8
[24]任彩丽李东亮赵红岗,等.全脑缺血-再灌注大鼠脑组织内源性硫化氢的动态变化[J].中华脑血管病杂志,2004,5：177-180.
[25]Unterberg AW, Stover J, Kress B, et al.edema and brain trauma.Neuroscience[J], 2004,129(4):1021-1029.
[26]Blackstone E, Roth MB. Suspended animation-like state protects mice from lethal hypoxia[J]. Shock.2007,27(4):370-372
[27]Haouzi P, Notet V,Chenuel B, et al. H2S induced hypometabolism in mice is missing in sedated sheep[J].Respir Physiol Neurobiol,2008,160(1),109-115.
[28]Elrod JW, Calvert JW, Morrison J, et al.Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function[J]. Proc Natl Acad Sci,2007,104(39):15560-15565.
[29]袁毅,雷立芳,涂秋云,等.大鼠脑缺血再灌注中血脑屏障通透性的改变与基质金属蛋白酶9表达的关系[J].Chin J Arterioscler,2008,16(7):510-512.
[30]郭芮兵,刘新峰。疾病状态下血-脑屏障的病理性开放[J].医学研究生学报,2005,18(8)：743-745
[31]Xiao F. Bench to bedside:brain edema and cerebral resuscitation:the present and future[J]. Acad Emerg Med,2002,9(9):933-946.
[32]Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation[J].Faseb,2006,20(12):2118-2120.
[33]邵建林,王俊,科马虹,等.外源性硫化氢对脑缺血再灌注损伤大鼠海马气体信号分子的影响[J].中华麻醉学杂志,2007,27(5)：451-454.
[34]Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343 (1):303-310.
[35]黄亮,刘雪兰,曹春水,等.依达拉奉对心肺复苏后脑水通道蛋白-4表达的影响[J].中华急诊医学杂志,2008,17(7)696-700.
[36]Duggal N, Schmidt Kastner R, HaKim AM. Nestin expression in reactive astrocytes following focal cerebral ischemia in rats[J]. Brain Res,1997,768(1-2):1-9.
[37]Krum JM, Rosenstein JM. Transient coexpression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds[J]. Exp Neurol,1999,160 (2):348-360.
[38]Holmin S, Almqvist P, Lendahl U, et al. Adult nestin expressing subependymal cells differentiate to astrocytes in response to brain injury[J]. Eur J Neurosci,1997,9 (1):65-75.
[39]Lin RC, Matesic DF, Marvin M, et al. Reexpression of the intermediate filament nestin in reactive astrocytes [J]. Neurobiol Dis,1995,2 (2):79-85.
[40]张敬军,陈青.脑缺血再灌流后海马区细胞凋亡的研究[J].中国临床神经科学,1999,7(1)：1-2.
[41]Zhao W,Zhang J,Lu Y,et al. The vasorelaxant effect of H2S as a novel endogenous gaseous K (ATP) channel openei[J]. EMBO,2001,20(21):6008-6016.
[42]Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343(1):303-310.
[43]Papapetropoulos A, Pyriochou A, Altaany Z, etal.Hydrogen sulfide is an endogenous stimulator of angiogenesis[J]. PNAS,2009,106(51):21972-21977.
[44]苗晓蕾,嵇晴,李丹,硫化氢联合浅低温对大鼠脑缺血再灌注损伤的影响[J].中华麻醉学杂志,2010,30(9)：1122-1125
[45]Liu XH, Pan LL, Zhuo Y, etal.Hypoxia-Inducible Factor-1 is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress [J].Biol Pharm. Bull,2010,33(9):1550-1554.
[46]郭英,石德全,梁朝峰,等VEGF对大鼠海马回神经干细胞体外增殖和分化的影响[J].中国病理生理杂志,2007,23(10)：1914-1918.
[47]Geoadin RG, Sherman DL, Christian Hansen H, et al. Neurological recovery by EEG bursting after resuscitation from cardiac arrest in rats[J]. Resuscitation,2002,55(2):193-200.
[48]Xiao F,Arnold T,Zhang S, et al. Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats[J]. Acta Neurochir Suppl,2003,86:75-78.
[1].Eto K,Ogasawara M,Umemura K,et al.Hydrogen sulfide is produced in response to neuronal excitation [J]. Neuroscience,2002,22(9):3386-3391
[2].Shibuya N,Tanaka M,Yoshida M,et al.3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J].Antioxid Redox signal 2009, 11(4):703-714.
[3].Lowicka E,Beltowski J.Hydrogen sulfide(H2S)-the third gas of interest for pharmacologists [J]. Pharmacological Rep.2007,59(l):4-24.
[4].Belardinelli MC,Chabli A,Chadefaux-Vekemans B,et al.Urinary sulfur compounds in down syndrome[J].clin chem,2001,47(8):1500-1501.
[5].Fume J,Springfield J,Koening T,et al.Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues:A specialized function of the colonic mucosa[J].Biochem Pharmacol,2001,62(2):255-259.
[6].Beauchamp RO,Jr,Bus JS, Popp JA,et al.A Critical review of the literature of the literature on hydrogen sulfide toxicity[J].Crit Rev Toxicol,1984,13(1):25-97.
[7].任彩丽李东亮赵红岗,等.全脑缺血-再灌注大鼠脑组织内源性硫化氢的动态变化[J].中华脑血管病杂志.2008,5(4)：177-180
[8].任彩丽,赵红岗,刘磊,等.缺氧缺血性脑损伤新生大鼠皮质脑组织硫化氢的动态变化[J].实用儿科临床杂志变化,2006,23(12)：930-931.
[9].蔺际龚,魏红艳,李慧,等.大鼠心肺复苏后血清硫化氢浓度变化[J].细胞与分子免疫学杂志,2010,26(4)：363-365.
[10].Tay A, Hu L, Lu M, et al. Hydrogen sulifde protects neuroues against hypoxicinjury via stimulation of ATP-senstive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway [J].Neuroscience,2010,167(2): 277-286.
[11]. Ren C, Du A, Li D,et al. Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats[J].Brain Res,2010,1235:197-205.
[12].Zhao W,Zhang J,Lu Y,et al. The vasorelaxant effect of H2S as a novel endogenous gaseous K (ATP) channel opener[J]. EMBO,2001,20(21):6008-6016.
[13].Lee M, Schwab C, Yu S,et al. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide[J]. Neurobiology of Aging,2009,30(10):1523-1534.
[14].Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation[J].Faseb,2006,20(12):2118-2120.
[15].邵建林,王俊,科马虹,等.外源性硫化氢对脑缺血再灌注损伤大鼠海马气体信号分子的影响[J].中华麻醉学杂志,2007,27(5)：451-454.
[16]. Bhatia M,Wong FL,Fu D, et al.Role of hydrogen sulfide in acute pancreatitis and associated lung injury [J]. The FASEB,2005,19(6):623-625.
[17].Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343 (1):303-310.
[18].Kimura Y,Kimura H.Hydrogen sulfide protects neurons from oxidative stress[J].FASEB, 2004,18(10):1165-1167.
[19].邵建林,王铃玲,王俊科,等.H2S通过cAMP介导Ph K/Akt/P70s6K通路抑制缺氧/复氧后神经元的凋亡[J].中国病理生理杂志,2007,23(12)：2317-2321.
[20].Kimura H, Hydrogen Sulfide Induces Cyclic AMP and Modulates the NMDA Receptor [J].Biochem Biophysical Res Commun,2000,267(1):129-133.
[21].张自立,蔺际,廖晓星,等。硫化氢对大鼠心脏骤停后海马组织bax和bcl-2表达的影响[J].中国急救医学,2011,31(1)：36-39.
[22].Yin WL, Qin J, Hu HB, et al.Hydrogen sulfide inhibits MPP+-induced apoptosis in PC 12 cells[J].Life Sciences,2009,85(7-8):269-275.
[23].Cheung NS, Peng ZF, Chen MJ,et al.Hydrogen sulfide induced neuronal death occurs via glutamate receptor and is associated with calpain activation and lysosomal rupture in mouse primary cortical neurons[J].Neuropharmacology,2007,53(4):505-514.
[24].Blackstone E, Morrison M, Roth MB., et al.H2S Induces a Suspended Animation-Like State in Mice[J].Brevia,2005,308(22):518.
[25].Haouzi P, Notet V,Chenuel B, et al. H2S induced hypometabolism in mice is missing in sedated sheep[J].Respir Physiol Neurobiol,2008,160(1),109-115.
[26].Tyagi N, Givvimani S, Qipshidze N,et al.Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice[J].Neurochem Int,2010,56(2):301-307.
[27].Abe K, Kimura K.The possible role of hydrogen sulfide as an endogenous neuromodulator[J]. Neurosci,1996,16(3):1066-1071.
[28].Lu M,Hu LF,Hu G,et al.Hydrogen sulfide protects astrocytes against H2O2-induced neural injury via enhancing glutamate uptake[J].Free Radic Biol Med,2008,45(12):1705-1713.
[29].Liu X, Pan L, Zhuo Y, et al.Hypoxia-Inducible Factor-1 is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic StressBiol[J]. Pharm. Bull,2010,33(9): 1550-1554.
[30].Minamishima S,Bougaki M,Sips PY,etal.Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice[J].Circulation,2009,120(10):888-896.
[2]Chad K, Nicholson,JohnW.Calvert.Hydrogen sulfide and ischemia-reperfusion injury[J]. Pharmacol Res,2010,62(4):289-297.
[3]Lee M, Schwab C, Yu S,et al. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide[J]. Neurobiol Aging,2009,30 (10):1523-1534.
[4]Kimura Y,Kimura H.Hydrogen sulfide protects neurons from oxidative stress[J]. FASEB,2004,18(10):1165-1167.
[5]Tyagi N,Givvimani S, Qipshidze N,et al.Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice[J].Neurochem Int,2010,56(2):301-307.
[6]Tay AS, Hu LF, Lu M, et al. Hydrogen sulifde protects neuroues against hypoxicinjury via stimulation of ATP-senstive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway [J].Neuroscience,2010,167(2):277-286.
[7]Ren CL, Du AL, Li DL,et al. Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats[J].Brain Research,2010,12345:197-205.
[8]Minamishima S,Bougaki M,Sips PY.etal.Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice[J].circulation,2009,120(10):888-896.
[9]Papapetropoulos A, Pyriochou A, Altaany Z, etal.Hydrogen sulfide is an endogenous stimulator of angiogenesis[J]. PNAS,2009,106(51):21972-21977.
[10]Xiao F,Zhang S,Arnold TC,et al. Mild hypothemfia induced before cardiac arrest reduces brain edema formation in rats[J].Acad Emerg Med,2002,9(2):105-114.
[11]郭梅凤,刘励军,徐信发,等.大鼠心肺复苏后脑组织含水量和水通道蛋白-4的动态变化及相关性研究[J].中国急救医学,2006,26(9)：673-674.
[12]王姗姗,陈寿权,李章平,等。乌司他丁对心肺复苏后大鼠脑水肿和血脑屏障的作用[J],中华急诊医学杂志,2006,15(4)：338-341.
[13]Geocadin RG, Ghodadra R, Kimura T,et al. A novel quantitative EEG injury measure of global cerebral ischemia. Clin Neurophysiol,2000,111 (10):1779-1787
[14]Von Planta I,Weil MH,Von Planta M,et al.Cardiopulmonary resuscitation in the rat[J].J Appl Physiol,1988,65(6):2641-2647.
[15]Hans HL, Hendrickx, Rao GR, et al. Asphyxia cardiac arrest and resuscitation [J].Chin J Emery Med,2002,12(2):97-116.
[16]陈寿权,李章平,王姗姗,等.窒息法致大鼠心脏骤停模型复苏的影响因素[J].中华急诊医学[J],2005,14(10)：814-817.
[17]孟庆义,马勇,钱远宇,等.氨茶碱和肾上腺素对大鼠心脏停搏的作用[J].中华急诊医学,2005,14(6)：482-484.
[18]Hendrickx HHL, Rao GR, Safar P, et al. Asphyxia cardiac arrest and resuscitation in rats[J].Resuscitation,1984,12(2):97-116.
[19]American Heart Association.Utstein-Style Guidelines for Uniform Reporting of Laboratory CPR Research[J]. Circulation,1996,94:232-233.
[20]Schneider A, Bottiger BW, Popp E. Cerebral Resuscitation After Cardiocirculatory Arrest[J].AnesthAnalg,2009,108(3):971-979.
[21]Shibuya N,Tanaka M,Yoshida M,et al.3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J].Antioxid Redox signal 2009, 11(4):703-714.
[22]Wang R.Twos conpany,threes acrowd:can H2S be the third endogenous transmitter? [J].FASEB,2002,16(13):1792-1798.
[23]Eto K, Asada T, Arima K, Makifuchi T, Brain hydrogen sulfide is severely decreased in Alzheimer's disease[J].Biochem Biophys Res Commun,2002 24;293(5):1485-8
[24]任彩丽李东亮赵红岗,等.全脑缺血-再灌注大鼠脑组织内源性硫化氢的动态变化[J].中华脑血管病杂志,2004,5：177-180.
[25]Unterberg AW, Stover J, Kress B, et al.edema and brain trauma.Neuroscience[J], 2004,129(4):1021-1029.
[26]Blackstone E, Roth MB. Suspended animation-like state protects mice from lethal hypoxia[J]. Shock.2007,27(4):370-372
[27]Haouzi P, Notet V,Chenuel B, et al. H2S induced hypometabolism in mice is missing in sedated sheep[J].Respir Physiol Neurobiol,2008,160(1),109-115.
[28]Elrod JW, Calvert JW, Morrison J, et al.Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function[J]. Proc Natl Acad Sci,2007,104(39):15560-15565.
[29]袁毅,雷立芳,涂秋云,等.大鼠脑缺血再灌注中血脑屏障通透性的改变与基质金属蛋白酶9表达的关系[J].Chin J Arterioscler,2008,16(7):510-512.
[30]郭芮兵,刘新峰。疾病状态下血-脑屏障的病理性开放[J].医学研究生学报,2005,18(8)：743-745
[31]Xiao F. Bench to bedside:brain edema and cerebral resuscitation:the present and future[J]. Acad Emerg Med,2002,9(9):933-946.
[32]Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation[J].Faseb,2006,20(12):2118-2120.
[33]邵建林,王俊,科马虹,等.外源性硫化氢对脑缺血再灌注损伤大鼠海马气体信号分子的影响[J].中华麻醉学杂志,2007,27(5)：451-454.
[34]Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343 (1):303-310.
[35]黄亮,刘雪兰,曹春水,等.依达拉奉对心肺复苏后脑水通道蛋白-4表达的影响[J].中华急诊医学杂志,2008,17(7)696-700.
[36]Duggal N, Schmidt Kastner R, HaKim AM. Nestin expression in reactive astrocytes following focal cerebral ischemia in rats[J]. Brain Res,1997,768(1-2):1-9.
[37]Krum JM, Rosenstein JM. Transient coexpression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds[J]. Exp Neurol,1999,160 (2):348-360.
[38]Holmin S, Almqvist P, Lendahl U, et al. Adult nestin expressing subependymal cells differentiate to astrocytes in response to brain injury[J]. Eur J Neurosci,1997,9 (1):65-75.
[39]Lin RC, Matesic DF, Marvin M, et al. Reexpression of the intermediate filament nestin in reactive astrocytes [J]. Neurobiol Dis,1995,2 (2):79-85.
[40]张敬军,陈青.脑缺血再灌流后海马区细胞凋亡的研究[J].中国临床神经科学,1999,7(1)：1-2.
[41]Zhao W,Zhang J,Lu Y,et al. The vasorelaxant effect of H2S as a novel endogenous gaseous K (ATP) channel openei[J]. EMBO,2001,20(21):6008-6016.
[42]Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343(1):303-310.
[43]Papapetropoulos A, Pyriochou A, Altaany Z, etal.Hydrogen sulfide is an endogenous stimulator of angiogenesis[J]. PNAS,2009,106(51):21972-21977.
[44]苗晓蕾,嵇晴,李丹,硫化氢联合浅低温对大鼠脑缺血再灌注损伤的影响[J].中华麻醉学杂志,2010,30(9)：1122-1125
[45]Liu XH, Pan LL, Zhuo Y, etal.Hypoxia-Inducible Factor-1 is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic Stress [J].Biol Pharm. Bull,2010,33(9):1550-1554.
[46]郭英,石德全,梁朝峰,等VEGF对大鼠海马回神经干细胞体外增殖和分化的影响[J].中国病理生理杂志,2007,23(10)：1914-1918.
[47]Geoadin RG, Sherman DL, Christian Hansen H, et al. Neurological recovery by EEG bursting after resuscitation from cardiac arrest in rats[J]. Resuscitation,2002,55(2):193-200.
[48]Xiao F,Arnold T,Zhang S, et al. Matrix metalloproteinases are not involved in early brain edema formation after cardiac arrest in rats[J]. Acta Neurochir Suppl,2003,86:75-78.
[1].Eto K,Ogasawara M,Umemura K,et al.Hydrogen sulfide is produced in response to neuronal excitation [J]. Neuroscience,2002,22(9):3386-3391
[2].Shibuya N,Tanaka M,Yoshida M,et al.3-mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J].Antioxid Redox signal 2009, 11(4):703-714.
[3].Lowicka E,Beltowski J.Hydrogen sulfide(H2S)-the third gas of interest for pharmacologists [J]. Pharmacological Rep.2007,59(l):4-24.
[4].Belardinelli MC,Chabli A,Chadefaux-Vekemans B,et al.Urinary sulfur compounds in down syndrome[J].clin chem,2001,47(8):1500-1501.
[5].Fume J,Springfield J,Koening T,et al.Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues:A specialized function of the colonic mucosa[J].Biochem Pharmacol,2001,62(2):255-259.
[6].Beauchamp RO,Jr,Bus JS, Popp JA,et al.A Critical review of the literature of the literature on hydrogen sulfide toxicity[J].Crit Rev Toxicol,1984,13(1):25-97.
[7].任彩丽李东亮赵红岗,等.全脑缺血-再灌注大鼠脑组织内源性硫化氢的动态变化[J].中华脑血管病杂志.2008,5(4)：177-180
[8].任彩丽,赵红岗,刘磊,等.缺氧缺血性脑损伤新生大鼠皮质脑组织硫化氢的动态变化[J].实用儿科临床杂志变化,2006,23(12)：930-931.
[9].蔺际龚,魏红艳,李慧,等.大鼠心肺复苏后血清硫化氢浓度变化[J].细胞与分子免疫学杂志,2010,26(4)：363-365.
[10].Tay A, Hu L, Lu M, et al. Hydrogen sulifde protects neuroues against hypoxicinjury via stimulation of ATP-senstive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway [J].Neuroscience,2010,167(2): 277-286.
[11]. Ren C, Du A, Li D,et al. Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats[J].Brain Res,2010,1235:197-205.
[12].Zhao W,Zhang J,Lu Y,et al. The vasorelaxant effect of H2S as a novel endogenous gaseous K (ATP) channel opener[J]. EMBO,2001,20(21):6008-6016.
[13].Lee M, Schwab C, Yu S,et al. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide[J]. Neurobiology of Aging,2009,30(10):1523-1534.
[14].Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation[J].Faseb,2006,20(12):2118-2120.
[15].邵建林,王俊,科马虹,等.外源性硫化氢对脑缺血再灌注损伤大鼠海马气体信号分子的影响[J].中华麻醉学杂志,2007,27(5)：451-454.
[16]. Bhatia M,Wong FL,Fu D, et al.Role of hydrogen sulfide in acute pancreatitis and associated lung injury [J]. The FASEB,2005,19(6):623-625.
[17].Whiteman M, Li L, Kostetski I, et al. Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide[J]. Biochem Biophys Res Commun,2006,343 (1):303-310.
[18].Kimura Y,Kimura H.Hydrogen sulfide protects neurons from oxidative stress[J].FASEB, 2004,18(10):1165-1167.
[19].邵建林,王铃玲,王俊科,等.H2S通过cAMP介导Ph K/Akt/P70s6K通路抑制缺氧/复氧后神经元的凋亡[J].中国病理生理杂志,2007,23(12)：2317-2321.
[20].Kimura H, Hydrogen Sulfide Induces Cyclic AMP and Modulates the NMDA Receptor [J].Biochem Biophysical Res Commun,2000,267(1):129-133.
[21].张自立,蔺际,廖晓星,等。硫化氢对大鼠心脏骤停后海马组织bax和bcl-2表达的影响[J].中国急救医学,2011,31(1)：36-39.
[22].Yin WL, Qin J, Hu HB, et al.Hydrogen sulfide inhibits MPP+-induced apoptosis in PC 12 cells[J].Life Sciences,2009,85(7-8):269-275.
[23].Cheung NS, Peng ZF, Chen MJ,et al.Hydrogen sulfide induced neuronal death occurs via glutamate receptor and is associated with calpain activation and lysosomal rupture in mouse primary cortical neurons[J].Neuropharmacology,2007,53(4):505-514.
[24].Blackstone E, Morrison M, Roth MB., et al.H2S Induces a Suspended Animation-Like State in Mice[J].Brevia,2005,308(22):518.
[25].Haouzi P, Notet V,Chenuel B, et al. H2S induced hypometabolism in mice is missing in sedated sheep[J].Respir Physiol Neurobiol,2008,160(1),109-115.
[26].Tyagi N, Givvimani S, Qipshidze N,et al.Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice[J].Neurochem Int,2010,56(2):301-307.
[27].Abe K, Kimura K.The possible role of hydrogen sulfide as an endogenous neuromodulator[J]. Neurosci,1996,16(3):1066-1071.
[28].Lu M,Hu LF,Hu G,et al.Hydrogen sulfide protects astrocytes against H2O2-induced neural injury via enhancing glutamate uptake[J].Free Radic Biol Med,2008,45(12):1705-1713.
[29].Liu X, Pan L, Zhuo Y, et al.Hypoxia-Inducible Factor-1 is Involved in the Pro-angiogenic Effect of Hydrogen Sulfide under Hypoxic StressBiol[J]. Pharm. Bull,2010,33(9): 1550-1554.
[30].Minamishima S,Bougaki M,Sips PY,etal.Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice[J].Circulation,2009,120(10):888-896.