褪黑素在细菌脂多糖引起胎鼠脑细胞钙超载中的神经保护作用
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摘要
目的:通过给妊娠第19天SD孕鼠腹腔注射细菌脂多糖,观察褪黑素对急性分离胎鼠脑细胞内游离钙的影响,探讨褪黑素对脑损伤的保护作用。
方法:72只SD孕鼠随机分为:LPS处理组(LPS组)、MT处理组(MT组)、空白对照组,每组24只孕鼠。LPS组和空白对照组分别予腹腔注射LPS(500μg/kg)和等容积生理盐水;MT组孕鼠同时腹腔注射LPS 500μg/kg +MT 10mg/kg。分别于给药后1h、6h、12h、24h、48h、72h剖腹取出胎鼠,急性分离脑组织,新型荧光探针Fluo-3/AM负载胎鼠脑细胞,流式细胞术检测胎鼠细胞内游离钙的平均荧光强度。
结果:
1、LPS组各小组随着注药后观察时间的延长,脑细胞钙离子荧光值于6h开始明显上升,12h达到高峰,各时间点均明显高于对照组(P<0.001),具有统计学差异。且1h与6h、6h与12h、12h与24h、24h与48h,P均<0.05,均有统计学意义;48h与72h比较,P >0.05,无统计学差异,但仍呈上升趋势。
2、MT组72h与LPS组72h组比较P>0.05,无统计学意义,但其值低于LPS组,6h、12h分别与LPS组比较P <0.001,其余各时间点钙离子荧光值均低于LPS组(P <0.05),差异有统计学意义。
结论:
1、脂多糖通过诱导胎鼠脑细胞内钙离子超载,导致脑损伤。
2、细胞内钙超载是胎鼠脑细胞损伤机制的一个重要环节。
3、褪黑素通过抑制细胞内钙超载,对脂多糖诱导的胎鼠脑细胞损伤有保护作用。随着对新生儿缺血缺氧性脑病(HIE)发病机制研究的不断深入,这将为HIE脑损伤的保护治疗提供新的策略与方法。
Objective : To observe the effects of intracellular calcium in the brain cells of acutely isolated fetal mouse and investigate the protection of melatonin on brain injury, by injecting lipopolysaccharide in the abdomen of SD pregnant rats of 19 days of pregnancy.
Methods: The 72 pregnant Sprague-Dawley rats of 19 days of pregnancy were divided randomly into three groups:the intrauterine infection group (LPS group), the melatonin group (MT group) and the blank control group, 24 in each group. In LPS group, the pregnant rats received an intraperitoneal (i.p.) injection of LPS (500μg/kg). the control group injected with saline intraperitoneally. In MT group, the rats were treated with LPS 500μg/kg and MT 10 mg/kg simultaneously. Then, the fetuses were removed by laparotomy, according to the time after injection, respectively: 1h、6h、12h、24h、48h、72h, and the brain tissues were isolated acutely. Novel fluorescent probe Fluo-3/AM loaded fetal rat brain cells. The average fluorescence intensity of intracellular calcium of fetal rats was detected by flow cytometry.
Results:
1. With the observation time of injected LPS group, the calcium fluorescence values of brain cells are significantly increased at 6h and peaked at 12h, were significantly higher (P<0.001)at different time points. And 1h and 6h compared, 6h and 12h compared, 12h and 24h compared, 24h and 48h compared, all P<0.05; 48h and 72h compared, P>0.05, but still on an upward trend.
2. The value of calcium fluorescence in the MT group at 72h is lower than the LPS group at 72h, but is not statistically significant (P>0.05), The value of calcium fluorescence in the MT group at 6h and 12h is significantly lower than the LPS group (P<0.001), the calcium fluorescence of other groups at each time point were significantly lower than LPS group (P<0.05).
Conclusions:
1. LPS result in brain damage by inducing intracellular calcium overload in brain cells of fetal rat.
2. Intracellular calcium overload is an important part of the mechanism of brain cell injury of fetal rat.
3. Melatonin has a protective effect on lipopolysaccharide-induced brain cells injury of fetal rat by inhibiting intracellular calcium overload. With the deepening of the study on the pathogenesis of HIE, which will provide a new treatment strategies and methods for the protection of brain injury in HIE.
方法:72只SD孕鼠随机分为:LPS处理组(LPS组)、MT处理组(MT组)、空白对照组,每组24只孕鼠。LPS组和空白对照组分别予腹腔注射LPS(500μg/kg)和等容积生理盐水;MT组孕鼠同时腹腔注射LPS 500μg/kg +MT 10mg/kg。分别于给药后1h、6h、12h、24h、48h、72h剖腹取出胎鼠,急性分离脑组织,新型荧光探针Fluo-3/AM负载胎鼠脑细胞,流式细胞术检测胎鼠细胞内游离钙的平均荧光强度。
结果:
1、LPS组各小组随着注药后观察时间的延长,脑细胞钙离子荧光值于6h开始明显上升,12h达到高峰,各时间点均明显高于对照组(P<0.001),具有统计学差异。且1h与6h、6h与12h、12h与24h、24h与48h,P均<0.05,均有统计学意义;48h与72h比较,P >0.05,无统计学差异,但仍呈上升趋势。
2、MT组72h与LPS组72h组比较P>0.05,无统计学意义,但其值低于LPS组,6h、12h分别与LPS组比较P <0.001,其余各时间点钙离子荧光值均低于LPS组(P <0.05),差异有统计学意义。
结论:
1、脂多糖通过诱导胎鼠脑细胞内钙离子超载,导致脑损伤。
2、细胞内钙超载是胎鼠脑细胞损伤机制的一个重要环节。
3、褪黑素通过抑制细胞内钙超载,对脂多糖诱导的胎鼠脑细胞损伤有保护作用。随着对新生儿缺血缺氧性脑病(HIE)发病机制研究的不断深入,这将为HIE脑损伤的保护治疗提供新的策略与方法。
Objective : To observe the effects of intracellular calcium in the brain cells of acutely isolated fetal mouse and investigate the protection of melatonin on brain injury, by injecting lipopolysaccharide in the abdomen of SD pregnant rats of 19 days of pregnancy.
Methods: The 72 pregnant Sprague-Dawley rats of 19 days of pregnancy were divided randomly into three groups:the intrauterine infection group (LPS group), the melatonin group (MT group) and the blank control group, 24 in each group. In LPS group, the pregnant rats received an intraperitoneal (i.p.) injection of LPS (500μg/kg). the control group injected with saline intraperitoneally. In MT group, the rats were treated with LPS 500μg/kg and MT 10 mg/kg simultaneously. Then, the fetuses were removed by laparotomy, according to the time after injection, respectively: 1h、6h、12h、24h、48h、72h, and the brain tissues were isolated acutely. Novel fluorescent probe Fluo-3/AM loaded fetal rat brain cells. The average fluorescence intensity of intracellular calcium of fetal rats was detected by flow cytometry.
Results:
1. With the observation time of injected LPS group, the calcium fluorescence values of brain cells are significantly increased at 6h and peaked at 12h, were significantly higher (P<0.001)at different time points. And 1h and 6h compared, 6h and 12h compared, 12h and 24h compared, 24h and 48h compared, all P<0.05; 48h and 72h compared, P>0.05, but still on an upward trend.
2. The value of calcium fluorescence in the MT group at 72h is lower than the LPS group at 72h, but is not statistically significant (P>0.05), The value of calcium fluorescence in the MT group at 6h and 12h is significantly lower than the LPS group (P<0.001), the calcium fluorescence of other groups at each time point were significantly lower than LPS group (P<0.05).
Conclusions:
1. LPS result in brain damage by inducing intracellular calcium overload in brain cells of fetal rat.
2. Intracellular calcium overload is an important part of the mechanism of brain cell injury of fetal rat.
3. Melatonin has a protective effect on lipopolysaccharide-induced brain cells injury of fetal rat by inhibiting intracellular calcium overload. With the deepening of the study on the pathogenesis of HIE, which will provide a new treatment strategies and methods for the protection of brain injury in HIE.
引文
[1] Nicholson C, Bruggencate GT, Steinberg R, et al. Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette. Proc Natl Acad Sci USA, 1977, 74: 1287-1290.
[2] Schurr A, Rigor BM. The mechanism of cerebral hypoxic-ischemic damage.Hippocampus, 1992, 2(3): 221-228
[3] Vannucci RC, Brucklacher RM, Vannucci SJ. Intracellular calcium accumulation during the evolusion of hypoxic-ischemic brain damage in the immature rat. Brain Res Dev Brain Res, 2001, 31, 126(1): 117-120.
[4] Etienne Manneville JB, Adamson P, et al. ICAM-1-coupled cytoskeletal tearrangements and transcendothelia in brain endothelial cell lines [J]. Immunol, 2000, 165(6): 3375-3383.
[5] Pisani AP, Calabesi P, Tozzi A, et al. L-type Ca2+ channel blockers attenuate electrical change and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons. Stroke,1998, 29: 196-202.
[6] Dorothee Ferger, Josef Krieglstein. Determination of intracellular Ca2+ concentration Can be a useful tool to predict neuronal damage and neuroprotective properties of drugs. Brain Res, 1996, 732: 87-94.
[7] Nakamura T, Minamisawa H, Katayama Y, et al. Increased intracellular Ca2+concentration in the hippocampal CAI area during global ischemia and reperfusion in the rat : a possible cause of delayed neuronal death.Neuroscience, 1999, 88 (1): 57-67.
[8]陈康宁,董为伟.大鼠脑缺血/再灌流中钙与神经元凋亡关系的研究.中国老年学杂志,2000,20(7):293-295.
[9] Claustrat B,Brun J, Chazot G. basic physiology and pathophysiology of melatonin[J]. Sleep Med Rev, 2005, 9(1):11-24.
[10] Boguszewska A, Pastemak K. Melatonin and its biological significance[J]. Pol Merkuriusz Lek, 2004, 17(101):523-527.
[11] Pevet P. Melatonin:from seasonal to circadian sigual[J]. Neuroendocrinol,2003, 15(4):422-426.
[12] Salie R , Harper I , Cillie C , et al . Melatonin protect s against ischaemic-reperfusion myocardial damage[J ] . J Mol Cell Cardiol , 2001 ,33 (2) :343– 357.
[13]霍展祥,刘东华,刘晓丽.褪黑素对小鼠反复脑缺血再灌注损伤学习记忆的改善作用及机制[J].中国临床药理学与治疗学,2003, 8(5): 567-569.
[14] Cuzzocrea S, Reiter RJ. Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury [J]. Eur J Pharmaco1. 2001, 426(1-2): 1-10.
[15] Gen W, Tani M, Takeshita J, et a1. Mechanisms of Ca2+ ovedoad induced by extracelular H202 in quiescent isolated rat cardiomyocytes [J]. Basic Res Cardiol, 2001, 96(6): 623-629.
[16] Okatani Y, Watanabe K, Hayashi K, et a1. Melatonin suppresses vasospastic efect of hydrogen peroxide in human umbilical artery: relation to calcium influx [J]. J Pineal Res. 1997, 22(4):232-237.
[17] Paredes RM, Etzler JC, Watts LT, et al. Chemical calcium indicators. Methods. 2008; 46(3): 143-151.
[18] Loughrey CM, MacEachern KE, Cooper J, et al. Measurement of the dissociation constant of Fluo-3 for Ca2+ in isolated rabbit cardiomyocytes using Ca2+ wave characteristics. Cell Calcium. 2003,34(1):1-9.
[19] Xu Dx,Chen YH,Zhao L,et a1.Reactive oxygen species are involved in lipopolysaeeharide-induced intrauterine growth restriction and skeletal development retardation in mice[J].Am J Obstet Cyneeol,2006,195(6):1707-1714.
[20] Zhang Y,Croft KD,Moil TA ,et a1.The antioxidant tempol prevents and partially reverses dexamethasone induced hypertension in the rat[J].Am J Hypertens,2004,17(3):260-265.
[21]金胜威,张力,叶笃军.脂氧素对脂多糖诱导的巨噬细胞游离钙浓度变化及活性氧的影响[J].中国病理生理杂志,2005,21(8): 1651.
[22] Ben-Ari Z,Peppo O,Yitzhaki S,Cheporko Y,Shainberg A,Zinman T,Ravid A,ZemelR,Bachmator L,Kurzwald E,Mor E,Hochhauser E.Uridine-5’-triphate protects against hepatic-ischemic/reperfusion injury in mice.Transplantation.2009,87(8):1155-62.
[23] W an g X, W an g R, Fan Z, et a1. Thiamine deficiency induces endoplasmic reticulum stress in neurons[J].Neuroscience,2007,144(3):1045-1046.
[24] Das A,Gamer DP,del Re AM ,et a1. Calpeptin provides functional neuroprotecfion to rat retinal ganglion cells following Ca2+ influx[J].Brain Res,2006,1084(1):146-157.
[25] Schuh RA,Kristian T,Fiskum G.Calpeptindependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein(CREB)[J] . J Neurochem,2005,92(2):388-394.
[26] Kristian T.Metabolic stages mitochondria and calcium in hypoxic/ischemic brain damage[J].Cell Calcium,2004,36(3-4):221-233.
[27] Sobie EA, Kao JP, Lederer WJ. Novel approach to real-time flash photolysis and confocal [Ca2+] imaging. Pflugers Arch.2007;454(4):663-673.
[28] Plank DM, Sussman MA. Intracellular Ca2+ measurements in live cells by rapid line scan confocal microscopy: simplified calibration methodology. Methods Cell Sci. 2003;25(3-4):123-133.
[29]宋平根,李素文主编.流式细胞术的原理和应用.北京:北京师范大学出版社,1992 :78- 84.
[30] Barhwal K,Hota SK,Baitharu I,Prasad D,Singh SB,Ilavzhagan G.Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment:Complementary roles of L-type calcium channel and NMDA receptors.Neurobiol Dis.2009,34(2):230-44 .
[31] Haile M,Limson F,Gingrich K,Li YS,Quartermain D,Blanck T,Bekker A.Nimmodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice.J Neurosury Anesthesiol.2009,21(2):140-4.
[32]王萍,周伟.褪黑素的生物学作用及研究进展[J].国际儿科学杂志, 2007, 3 4(1): 69-72.
[33] Zhang Q, Zhang J. Effect of melatonin on the spatial end temporal changes of[Ca2+] in single living cells of cortical neurons by laser scarming confocal] microscopy [J].Chin Mod J, 2000,113(6): 558-62.
[34]潘秀兰,马东周,范天凤等.褪黑素对大鼠脑损伤的保护作用及机制研究[J].陕西医学杂志,2009(1):20-22.
[1] Sutherland BA, Shaw OM, Clarkson AN, et al. Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action[J]. FASEB J 2005;19 (2):258-260.
[2]喻明(综述),李小刚(审校).钙与出血性脑损伤的研究进展[J].中华医学写作杂志2005;12 (1):66-69.
[3]杨树源,杨新宇.急性脑创伤后继发性神经细胞损伤的研究进展[J].中华神经外科杂志2004;20 (2):91-95.
[4] Honig LS, Rosenberg RN. Apoptosis and neurologic disease[J]. Am J Med 2000;108 (4):317-330.
[5]刘石林,赵林.大鼠脑挫伤后脑不同部位组织内钙含量的变化[J].临床康复杂志2004;8 (13):2581-2583.
[6] Ferger D, Krieglstein J. Determination of intracellular Ca2+ concentration can be a useful tool to predict neuronal damage and neuroprotective properties of drugs[J]. Brain Res 1996;732 (1-2):87-94.
[7]张相彤,刘恩重,苏君.创伤后神经元细胞内游离钙的变化及其影响因素的研究[J].哈尔滨医科大学学报2002;36 (3):191-193.
[8] Buki A, Siman R, Trojanowski JQ, et al. The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury[J]. J Neuropathol Exp Neurol 1999;58 (4):365-375.
[9] Weber JT, Rzigalinski BA, Willoughby KA, et al. Alterations in calcium-mediated signal transduction after traumatic injury of cortical neurons[J]. Cell Calcium 1999;26 (6):289-299.
[10] Shapira Y, Lam AM, Artru AA, et al. Ketamine alters calcium and magnesium in brain tissue following experimental head trauma in rats[J]. J Cereb Blood Flow Metab 1993;13 (6):962-968.
[11] Lai X, Zhu W, Yuan G. [Kinetics of the Ca(2+)-activated K+ channel in Ca2+ induced cortex neurons damage][J]. Hua Xi Yi Ke Da Xue Xue Bao 1999;30 (2):151-154.
[12] Shi R, Qiao X, Emerson N, et al. Dimethylsulfoxide enhances CNS neuronal plasma membrane resealing after injury in low temperature or low calcium[J]. J Neurocytol 2001;30 (9-10):829-839.
[13]余华,高峰.谷氨酸对培养大鼠皮层冲经细胞的毒性作用[J].浙江医学2002;24 (8):471-472.
[14] Chen HH, Wei CT, Chan MH. Neonatal toluene exposure alters glutamate-induced calcium signaling in developing cerebellar granule neurons[J]. Ann N Y Acad Sci 2004;1025:556-560.
[15] Bedford RF, Dacey R, Winn HR, et al. Adverse impact of a calcium entry-blocker (verapamil) on intracranial pressure in patients with brain tumors[J]. J Neurosurg 1983;59 (5):800-802.
[16] Harris RJ, Branston NM, Symon L, et al. The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia[J]. Stroke 1982;13 (6):759-766.
[17]马景鉴,杨树源.尼莫地平在治疗颅脑损伤中的作用[J].中华创伤杂志1991;7 (3):129-131.
[18]徐如祥,易声禹,吴声伶, et al.神经细胞Ca2+通道变化及对鼠血脑屏障通透性和外伤性脑水肿的影响[J].中华神经外科杂志1992;8 (1):41-44.
[19] Bailey I, Bell A, Gray J, et al. A trial of the effect of nimodipine on outcome after head injury[J]. Acta Neurochir (Wien) 1991;110 (3-4):97-105.
[20] Hadley MN, Martin NA, Spetzler RF, et al. Multiple intracranial aneurysms due to Coccidioides immitis infection. Case report[J]. J Neurosurg 1987;66 (3):453-456.
[2] Schurr A, Rigor BM. The mechanism of cerebral hypoxic-ischemic damage.Hippocampus, 1992, 2(3): 221-228
[3] Vannucci RC, Brucklacher RM, Vannucci SJ. Intracellular calcium accumulation during the evolusion of hypoxic-ischemic brain damage in the immature rat. Brain Res Dev Brain Res, 2001, 31, 126(1): 117-120.
[4] Etienne Manneville JB, Adamson P, et al. ICAM-1-coupled cytoskeletal tearrangements and transcendothelia in brain endothelial cell lines [J]. Immunol, 2000, 165(6): 3375-3383.
[5] Pisani AP, Calabesi P, Tozzi A, et al. L-type Ca2+ channel blockers attenuate electrical change and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons. Stroke,1998, 29: 196-202.
[6] Dorothee Ferger, Josef Krieglstein. Determination of intracellular Ca2+ concentration Can be a useful tool to predict neuronal damage and neuroprotective properties of drugs. Brain Res, 1996, 732: 87-94.
[7] Nakamura T, Minamisawa H, Katayama Y, et al. Increased intracellular Ca2+concentration in the hippocampal CAI area during global ischemia and reperfusion in the rat : a possible cause of delayed neuronal death.Neuroscience, 1999, 88 (1): 57-67.
[8]陈康宁,董为伟.大鼠脑缺血/再灌流中钙与神经元凋亡关系的研究.中国老年学杂志,2000,20(7):293-295.
[9] Claustrat B,Brun J, Chazot G. basic physiology and pathophysiology of melatonin[J]. Sleep Med Rev, 2005, 9(1):11-24.
[10] Boguszewska A, Pastemak K. Melatonin and its biological significance[J]. Pol Merkuriusz Lek, 2004, 17(101):523-527.
[11] Pevet P. Melatonin:from seasonal to circadian sigual[J]. Neuroendocrinol,2003, 15(4):422-426.
[12] Salie R , Harper I , Cillie C , et al . Melatonin protect s against ischaemic-reperfusion myocardial damage[J ] . J Mol Cell Cardiol , 2001 ,33 (2) :343– 357.
[13]霍展祥,刘东华,刘晓丽.褪黑素对小鼠反复脑缺血再灌注损伤学习记忆的改善作用及机制[J].中国临床药理学与治疗学,2003, 8(5): 567-569.
[14] Cuzzocrea S, Reiter RJ. Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury [J]. Eur J Pharmaco1. 2001, 426(1-2): 1-10.
[15] Gen W, Tani M, Takeshita J, et a1. Mechanisms of Ca2+ ovedoad induced by extracelular H202 in quiescent isolated rat cardiomyocytes [J]. Basic Res Cardiol, 2001, 96(6): 623-629.
[16] Okatani Y, Watanabe K, Hayashi K, et a1. Melatonin suppresses vasospastic efect of hydrogen peroxide in human umbilical artery: relation to calcium influx [J]. J Pineal Res. 1997, 22(4):232-237.
[17] Paredes RM, Etzler JC, Watts LT, et al. Chemical calcium indicators. Methods. 2008; 46(3): 143-151.
[18] Loughrey CM, MacEachern KE, Cooper J, et al. Measurement of the dissociation constant of Fluo-3 for Ca2+ in isolated rabbit cardiomyocytes using Ca2+ wave characteristics. Cell Calcium. 2003,34(1):1-9.
[19] Xu Dx,Chen YH,Zhao L,et a1.Reactive oxygen species are involved in lipopolysaeeharide-induced intrauterine growth restriction and skeletal development retardation in mice[J].Am J Obstet Cyneeol,2006,195(6):1707-1714.
[20] Zhang Y,Croft KD,Moil TA ,et a1.The antioxidant tempol prevents and partially reverses dexamethasone induced hypertension in the rat[J].Am J Hypertens,2004,17(3):260-265.
[21]金胜威,张力,叶笃军.脂氧素对脂多糖诱导的巨噬细胞游离钙浓度变化及活性氧的影响[J].中国病理生理杂志,2005,21(8): 1651.
[22] Ben-Ari Z,Peppo O,Yitzhaki S,Cheporko Y,Shainberg A,Zinman T,Ravid A,ZemelR,Bachmator L,Kurzwald E,Mor E,Hochhauser E.Uridine-5’-triphate protects against hepatic-ischemic/reperfusion injury in mice.Transplantation.2009,87(8):1155-62.
[23] W an g X, W an g R, Fan Z, et a1. Thiamine deficiency induces endoplasmic reticulum stress in neurons[J].Neuroscience,2007,144(3):1045-1046.
[24] Das A,Gamer DP,del Re AM ,et a1. Calpeptin provides functional neuroprotecfion to rat retinal ganglion cells following Ca2+ influx[J].Brain Res,2006,1084(1):146-157.
[25] Schuh RA,Kristian T,Fiskum G.Calpeptindependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein(CREB)[J] . J Neurochem,2005,92(2):388-394.
[26] Kristian T.Metabolic stages mitochondria and calcium in hypoxic/ischemic brain damage[J].Cell Calcium,2004,36(3-4):221-233.
[27] Sobie EA, Kao JP, Lederer WJ. Novel approach to real-time flash photolysis and confocal [Ca2+] imaging. Pflugers Arch.2007;454(4):663-673.
[28] Plank DM, Sussman MA. Intracellular Ca2+ measurements in live cells by rapid line scan confocal microscopy: simplified calibration methodology. Methods Cell Sci. 2003;25(3-4):123-133.
[29]宋平根,李素文主编.流式细胞术的原理和应用.北京:北京师范大学出版社,1992 :78- 84.
[30] Barhwal K,Hota SK,Baitharu I,Prasad D,Singh SB,Ilavzhagan G.Isradipine antagonizes hypobaric hypoxia induced CA1 damage and memory impairment:Complementary roles of L-type calcium channel and NMDA receptors.Neurobiol Dis.2009,34(2):230-44 .
[31] Haile M,Limson F,Gingrich K,Li YS,Quartermain D,Blanck T,Bekker A.Nimmodipine prevents transient cognitive dysfunction after moderate hypoxia in adult mice.J Neurosury Anesthesiol.2009,21(2):140-4.
[32]王萍,周伟.褪黑素的生物学作用及研究进展[J].国际儿科学杂志, 2007, 3 4(1): 69-72.
[33] Zhang Q, Zhang J. Effect of melatonin on the spatial end temporal changes of[Ca2+] in single living cells of cortical neurons by laser scarming confocal] microscopy [J].Chin Mod J, 2000,113(6): 558-62.
[34]潘秀兰,马东周,范天凤等.褪黑素对大鼠脑损伤的保护作用及机制研究[J].陕西医学杂志,2009(1):20-22.
[1] Sutherland BA, Shaw OM, Clarkson AN, et al. Neuroprotective effects of (-)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action[J]. FASEB J 2005;19 (2):258-260.
[2]喻明(综述),李小刚(审校).钙与出血性脑损伤的研究进展[J].中华医学写作杂志2005;12 (1):66-69.
[3]杨树源,杨新宇.急性脑创伤后继发性神经细胞损伤的研究进展[J].中华神经外科杂志2004;20 (2):91-95.
[4] Honig LS, Rosenberg RN. Apoptosis and neurologic disease[J]. Am J Med 2000;108 (4):317-330.
[5]刘石林,赵林.大鼠脑挫伤后脑不同部位组织内钙含量的变化[J].临床康复杂志2004;8 (13):2581-2583.
[6] Ferger D, Krieglstein J. Determination of intracellular Ca2+ concentration can be a useful tool to predict neuronal damage and neuroprotective properties of drugs[J]. Brain Res 1996;732 (1-2):87-94.
[7]张相彤,刘恩重,苏君.创伤后神经元细胞内游离钙的变化及其影响因素的研究[J].哈尔滨医科大学学报2002;36 (3):191-193.
[8] Buki A, Siman R, Trojanowski JQ, et al. The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury[J]. J Neuropathol Exp Neurol 1999;58 (4):365-375.
[9] Weber JT, Rzigalinski BA, Willoughby KA, et al. Alterations in calcium-mediated signal transduction after traumatic injury of cortical neurons[J]. Cell Calcium 1999;26 (6):289-299.
[10] Shapira Y, Lam AM, Artru AA, et al. Ketamine alters calcium and magnesium in brain tissue following experimental head trauma in rats[J]. J Cereb Blood Flow Metab 1993;13 (6):962-968.
[11] Lai X, Zhu W, Yuan G. [Kinetics of the Ca(2+)-activated K+ channel in Ca2+ induced cortex neurons damage][J]. Hua Xi Yi Ke Da Xue Xue Bao 1999;30 (2):151-154.
[12] Shi R, Qiao X, Emerson N, et al. Dimethylsulfoxide enhances CNS neuronal plasma membrane resealing after injury in low temperature or low calcium[J]. J Neurocytol 2001;30 (9-10):829-839.
[13]余华,高峰.谷氨酸对培养大鼠皮层冲经细胞的毒性作用[J].浙江医学2002;24 (8):471-472.
[14] Chen HH, Wei CT, Chan MH. Neonatal toluene exposure alters glutamate-induced calcium signaling in developing cerebellar granule neurons[J]. Ann N Y Acad Sci 2004;1025:556-560.
[15] Bedford RF, Dacey R, Winn HR, et al. Adverse impact of a calcium entry-blocker (verapamil) on intracranial pressure in patients with brain tumors[J]. J Neurosurg 1983;59 (5):800-802.
[16] Harris RJ, Branston NM, Symon L, et al. The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia[J]. Stroke 1982;13 (6):759-766.
[17]马景鉴,杨树源.尼莫地平在治疗颅脑损伤中的作用[J].中华创伤杂志1991;7 (3):129-131.
[18]徐如祥,易声禹,吴声伶, et al.神经细胞Ca2+通道变化及对鼠血脑屏障通透性和外伤性脑水肿的影响[J].中华神经外科杂志1992;8 (1):41-44.
[19] Bailey I, Bell A, Gray J, et al. A trial of the effect of nimodipine on outcome after head injury[J]. Acta Neurochir (Wien) 1991;110 (3-4):97-105.
[20] Hadley MN, Martin NA, Spetzler RF, et al. Multiple intracranial aneurysms due to Coccidioides immitis infection. Case report[J]. J Neurosurg 1987;66 (3):453-456.