督脉电针对不同时段急性颅脑损伤大鼠差异蛋白组学的研究
|
摘要
研究背景
颅脑损伤(craniocerebral injury, CCI)是一种致死率和致残率很高的疾病,在中国的发生率以及由其致伤致残、致死的伤员也逐年增加。目前,现代医学对颅脑损伤进行了大量研究,但没有重大突破,而针灸和中药具有一定的优势。
随着人类基因组草图序列测定的完成,基因组研究的重点也由结构基因组转向功能基因组,生命科学进入了蛋白质组学时代。差异蛋白组学的研究有利于人类更细致地研究疾病相关信息变化所导致的蛋白质种类和数量变化,有利于更深入地研究蛋白质的性质和功能,对探索疾病的真正发生机制具有极其重要的意义。在本课题的研究中,我们不是以颅脑损伤大鼠的血清为研究对象,而是对其脑组织进行差异蛋白组学研究,这更有利于揭示针刺治疗颅脑损伤的作用机制。
实验方法
135只SD雄性大鼠,随机分为三个时间段,空白组(24h、48h、6d)、模型组(24h、48h、6d)、电针组(24h、48h、6d),每组15只大鼠,共45只。参照Feeney等研制的鼠颅脑创伤模具改良式打击装置造模。电针“百会”、“印堂”督脉穴。术后24h、48h、6d取损伤区颅脑组织称重,保存。对样本蛋白进行提取、定量、蛋白双向电泳图像分析,找出差异点进行质谱分析和数据库检索。
实验结果
24h时间段有八个差异蛋白点共鉴定出6种蛋白质：烯醇化酶、白蛋白、腺苷酸激酶、结蛋白、半胱氨酸天冬氨酸特异性蛋白酶、锌指蛋白。
48h成功鉴定出7种蛋白质：假定蛋白、热休克蛋白8、微管蛋白β-5、锌指蛋白233、分泌颗粒素Ⅱ、醛缩酶A、热休克蛋白70。
6d时间段六个差异蛋白点共鉴定出4种蛋白质即电压依赖性阴离子通道
1、细胞角蛋白、锌指蛋白365、人转铁蛋白。
结论
通过本动物实验可见,电针可逆转颅脑损伤大鼠脑内多数差异蛋白表达的变化,其作用可能是通过抑制神经细胞凋亡、改善细胞能量代谢、调节异常蛋白等途径促进颅脑损伤的修复。随着时间和针刺次数的增加,电针可能逐渐侧重于发挥改善细胞能量代谢和抑制其凋亡的作用,而对受损蛋白的调节作用在减弱。
Background
Craniocerebral injury (craniocerebral injury, CCI) is a high mortality rate and morbidity of diseases, the incidence in our country and its injured and maimed, wounded also increased year by year of death. Currently, modern medicine has done a lot of traumatic brain injury, but no major breakthrough, but acupuncture and Chinese medicine has a definite advantage.
With the draft human genome sequence of the complete genome research shifted the focus from structural genomics functional genomics, life sciences into the proteomics era. Proteomics research is conducive to a more detailed study of human disease-related information resulting from changes in the type and quantity of protein changes that contribute to a more in-depth study of the nature and function of proteins, to explore the mechanism of disease, the real place of great importance.
In the study of this topic, we do not craniocerebral rats serum to study the object, but modifications to differentiate brain tissue proteomics science research, it more conducive to revealing the effect of acupuncture treatment of brain injury mechanisms.
Objective
to observe the effect of electroacupuncture(EA) on the differentially expressed proteins in the brain at different time courses after craniocerebral injury (CCI) in the rat, so as to study its underlying mechanism in improving craniocerebral injury.
Methods
A total of 135 male SD rats were randomized into normal control, model24h,EA24h,mode48h, EA48h, mode6d, EA6dgroups, with15 cases in each. CCI model was established by using modified Feeney'smethod. EA(2Hz,2-5mA)wasappliedtoBaiHui(GV20)and yintang(EX-4)for 30min. The injured brain tissue was collected 24h.48h and 6d after CCI and EA treatment, weighted and stored under-80℃till detection. Two dimensional gel electrophoresis(22DE) was used to separate total proteins of the brain tissue, followed by protein extraction and quantitation,2_D gel image analysis, matrix assisted laserdesorptionionisationtime-of-flightmassspec-trometry(MALDI-TOF-MS).
Results
24h successful identification of the six kinds of proteins:enolase、albumin、adenylate kinase、Desmin、Caspase、zinc finger protein;48h: successful identification of the seven kinds of proteins:hypothetical protein, heat shock protein 8, tubulinβ-5,233 zinc finger protein, secretory granulesⅡ, and Aldolase A, heat shock protein 70.6d period of six protein spots were identified four kinds of protein that is voltage dependent anion channel 1, cytokeratin, zinc finger protein 365, human transferrin.
Conclusion
Proteome analysis indicates that in CCI rats, some differentially expressed proteins involving energy metabolism, neuronal apoptosis reduction, protein degradation inhibition may contributeto the effect of EA in repairing the craniocerebral injury
颅脑损伤(craniocerebral injury, CCI)是一种致死率和致残率很高的疾病,在中国的发生率以及由其致伤致残、致死的伤员也逐年增加。目前,现代医学对颅脑损伤进行了大量研究,但没有重大突破,而针灸和中药具有一定的优势。
随着人类基因组草图序列测定的完成,基因组研究的重点也由结构基因组转向功能基因组,生命科学进入了蛋白质组学时代。差异蛋白组学的研究有利于人类更细致地研究疾病相关信息变化所导致的蛋白质种类和数量变化,有利于更深入地研究蛋白质的性质和功能,对探索疾病的真正发生机制具有极其重要的意义。在本课题的研究中,我们不是以颅脑损伤大鼠的血清为研究对象,而是对其脑组织进行差异蛋白组学研究,这更有利于揭示针刺治疗颅脑损伤的作用机制。
实验方法
135只SD雄性大鼠,随机分为三个时间段,空白组(24h、48h、6d)、模型组(24h、48h、6d)、电针组(24h、48h、6d),每组15只大鼠,共45只。参照Feeney等研制的鼠颅脑创伤模具改良式打击装置造模。电针“百会”、“印堂”督脉穴。术后24h、48h、6d取损伤区颅脑组织称重,保存。对样本蛋白进行提取、定量、蛋白双向电泳图像分析,找出差异点进行质谱分析和数据库检索。
实验结果
24h时间段有八个差异蛋白点共鉴定出6种蛋白质：烯醇化酶、白蛋白、腺苷酸激酶、结蛋白、半胱氨酸天冬氨酸特异性蛋白酶、锌指蛋白。
48h成功鉴定出7种蛋白质：假定蛋白、热休克蛋白8、微管蛋白β-5、锌指蛋白233、分泌颗粒素Ⅱ、醛缩酶A、热休克蛋白70。
6d时间段六个差异蛋白点共鉴定出4种蛋白质即电压依赖性阴离子通道
1、细胞角蛋白、锌指蛋白365、人转铁蛋白。
结论
通过本动物实验可见,电针可逆转颅脑损伤大鼠脑内多数差异蛋白表达的变化,其作用可能是通过抑制神经细胞凋亡、改善细胞能量代谢、调节异常蛋白等途径促进颅脑损伤的修复。随着时间和针刺次数的增加,电针可能逐渐侧重于发挥改善细胞能量代谢和抑制其凋亡的作用,而对受损蛋白的调节作用在减弱。
Background
Craniocerebral injury (craniocerebral injury, CCI) is a high mortality rate and morbidity of diseases, the incidence in our country and its injured and maimed, wounded also increased year by year of death. Currently, modern medicine has done a lot of traumatic brain injury, but no major breakthrough, but acupuncture and Chinese medicine has a definite advantage.
With the draft human genome sequence of the complete genome research shifted the focus from structural genomics functional genomics, life sciences into the proteomics era. Proteomics research is conducive to a more detailed study of human disease-related information resulting from changes in the type and quantity of protein changes that contribute to a more in-depth study of the nature and function of proteins, to explore the mechanism of disease, the real place of great importance.
In the study of this topic, we do not craniocerebral rats serum to study the object, but modifications to differentiate brain tissue proteomics science research, it more conducive to revealing the effect of acupuncture treatment of brain injury mechanisms.
Objective
to observe the effect of electroacupuncture(EA) on the differentially expressed proteins in the brain at different time courses after craniocerebral injury (CCI) in the rat, so as to study its underlying mechanism in improving craniocerebral injury.
Methods
A total of 135 male SD rats were randomized into normal control, model24h,EA24h,mode48h, EA48h, mode6d, EA6dgroups, with15 cases in each. CCI model was established by using modified Feeney'smethod. EA(2Hz,2-5mA)wasappliedtoBaiHui(GV20)and yintang(EX-4)for 30min. The injured brain tissue was collected 24h.48h and 6d after CCI and EA treatment, weighted and stored under-80℃till detection. Two dimensional gel electrophoresis(22DE) was used to separate total proteins of the brain tissue, followed by protein extraction and quantitation,2_D gel image analysis, matrix assisted laserdesorptionionisationtime-of-flightmassspec-trometry(MALDI-TOF-MS).
Results
24h successful identification of the six kinds of proteins:enolase、albumin、adenylate kinase、Desmin、Caspase、zinc finger protein;48h: successful identification of the seven kinds of proteins:hypothetical protein, heat shock protein 8, tubulinβ-5,233 zinc finger protein, secretory granulesⅡ, and Aldolase A, heat shock protein 70.6d period of six protein spots were identified four kinds of protein that is voltage dependent anion channel 1, cytokeratin, zinc finger protein 365, human transferrin.
Conclusion
Proteome analysis indicates that in CCI rats, some differentially expressed proteins involving energy metabolism, neuronal apoptosis reduction, protein degradation inhibition may contributeto the effect of EA in repairing the craniocerebral injury
引文
[1]张小年,张皓.创伤性颅脑损伤国内研究进展[J].中国康复理论与实践,2008,14(2)：101-104
[2]朱诚,江基尧. 中国颅脑创伤研究现状与展望. 中华神经外科杂志,1999；15：1-2.
[3]顾峻,顾红玉,陈玉英,等.MK-801对新生大鼠脑外伤后神经元凋亡的影响.解剖学杂志,2006；29：738-740.
[4]周伟缺氧缺血性脑损伤的分子生物学研究进展[J]国外医学·儿科学分册,1998,25(1)：33-35
[5]谭来勋,孙圣刚.大鼠脑外伤灶周突触和星形胶质细胞的变化及对GM1的反应.中国综合临床,2006；22：875-877.
[6]Oyesiku NM, Evans CO, Houston S,etaL.Regional changes in the expression of neurotrophic factors and their receptors following acute traumatic brain injury in the adult rat brain 1999, 833(2):161-172.
[7]Zou Huang LL, Hayes RLet al. Liposome - mediated NGF gene transfection following neuronal injury;potential therapeutic applications. Gene Ther,1999,6 (6):994-1005.
[8]王向东,张建生.急性颅脑损伤患者血清TGF2B1, TNF-α水平变化及意义[J].山东医药,2006,46(30)：8-10.
[9]Chen Y, Constantini s, Trembovler V, etal. An experimental model of closed head injury in mice pathpphysiology, histothology,and cognition deficits [J]. J Neurotmma,1996,13(10):557 - 568.
[10]费舟,易声禹.章翱,等重型颅呐损伤后钙调素与自由基水平变化及尼莫地平和脑活素的作用中华创伤杂志,1994；10(4)275-280
[11]Newcomb J. K, Zhao X, et al. Temporal profile of apoptosis-like changes in neurons and astrocytes following controlled cortical impact injury in the rat Experimental Neurology,1999,158(1):76-88.
[12]Wong J, Hoe NW, Zhiwei F, etaL Apoptosis and traumatic brain injury. Neurocrit Cat,2005,3(2):177-182.
[13]朱诚.中国颅脑创伤研究现状与展望[].中华神经外科杂志,1999,15(1)：1
[14]江基尧,朱诚.现代颅脑损伤学[].上海：第二军医大学出版社,1999.113-145
[15]贺晓生,易声禹,章翔,等,脑弥漫性轴索损伤轴索内钙超载及钙拮抗剂的治疗作用[J]中华神经外科杂志,2000,16(1)：482521
[16]Joly LM, Mueignat V, Mariani J. Plotk in the rat brain[J J. Ceteb Blood Flow Metab,2004,24:124-131
[17]Lei BF, TanJ, CaiHW. Etc of. effect of moderate hypotheromia liqid percuidation in brain tissue after cardiac arrest and resuscitation Stroke.1994,25(1):147 - 151
[18]陈锡群,龚孝淑,江基尧等,低温对实验型颅脑损伤大鼠免疫功能的影响[J]中华神经外科杂志,2001,17(3)：168-170.
[19]江基尧,朱诚.颅脑创伤临床救治指南[M].上海：第二军医大学出版社,2002：158-159
[20]池京洋,只达石,黄楹,等.亚低温治疗对重型颅脑损伤患者血中神经元特异性烯醇化酶的影响及其临床意义.中国急救医学,2006；26：659-660.
[21]李昊,郑珊,施伟.亚低温对幼猪外伤性脑损伤保护作用的研究中华小儿外科杂志,2006；27：424-427.
[22]王光伟,刘运生,赵林,等.亚低温对大鼠脑损伤后脑组织炎性反应的影响.中华创伤杂志,2005；21：443-446.
[1]Werner T. Promoters can contribute to the elucidation of protein function. Trends Biotechnaol,2003,21(1):9-13
[2]王伟,谢杰,方坚.督脉电针治疗脊髓损伤的研究进展.针灸临床杂志,2005,21(1)：60-62
[3]Dudrick SJ, Wilmore DW, Vars H, et al. Long time total parenteral nutrition with growth in puppies and positive nitrogen balance in patients [J]. Surgical Forum,1967,18:356-359.
[4]孙言伟,姜颖,贺福初.差异蛋白质组学的研究进展[J].生命科学,2005,17(2)：137-140.
[5]纪建国,茹炳根.蛋白质组学研究相关技术及其在生物医学研究中的应用[J].药物生物科技,2002,9(1)：121
[6]Steinberg TH, Haugland RP, Singer VL. App lications of SY2 PRO o range and SYPRO red p ro tein gel stains [J]. Anal Biochem.1996, 1; 239 (2):238-245
[7]FountoulakisM. Application of proteomics technologies inthe investigation of the brain. Mass Spectrom Rev,20023:231-258
[8]Kim SI, VosholH, vanOostrum J, et a.1 Neuroproteomics: expression profiling of the brain's proteomes in health anddisease. Neurochem Res,2004,29:1317-1331
[9]Conti A, Sanchez Ruiz Y, Bachi A, etal. Proteome study of humancerebrospinal fluid following traumatic brain injury indicates fibrin(ogen)degralation products as trauma-associated markers [J]. J Neurotrauma,2004.21(7):854-863.
[10]J Jenkins Lw, Pete-GW, Dixon CE, et 81. Conventional and functionalproteomics using large format two-dimensional gel electrophoresis 24 hoursafter controlled oorfieal impact in postnatal day 17 rats[J]. J Neurotrauma,2002,19(6):715-740.
1.丁晶闭合性颅脑损伤术后针刺治疗的疗效对比观察中国针灸,1996,11：11
2.杨晓燕.针刺治疗脑出血60例临床观察[J].天津中医药,2005；22(4)： 286.
3.雷磊.针刺治疗闭合性颅脑损伤52例临床观察中国针灸,1997,3：1731
4.张卓,等.针灸推拿配合开颅血肿清除术治疗高血压性脑出血偏瘫 后遗症48例[J].辽宁中医杂志,2006；33(11)：1487
5. Counsel 1C. Boonykamkul S, Dennisi, et al. Primary in cerebralhae morrhage in the Oxfordshir communi ty Stroke prOjeet: prognosi S[J]. Cerebmvasc OiS,1995; 5(1):262-271
6.靳淼,侯文静.针刺治疗高血压性脑出血早期96例[J].山东中医杂志,2002,21(6)：347
7.东贵荣.头穴针刺对急性脑出血大鼠痛反应神经元电活动的双向调节.中国临床康复.2006,10(20)48-50.
8.吴逊.第二次全国脑电图与临床神经生理学术会议论文综述[J].脑电图学与神经精神疾病杂志,1990,6(2)：95
9.东贵荣.急性脑出血病人运动诱发电位的临床研究[C].第五届全国肌电图及诱发电位学术会议论文集,北京：1993
10. 钟长明,林洪茂,刘庆芳,等.针刺与肌张力平衡促通法对中风偏瘫患者早期康复的作用[J].中国康复医学杂志,2001；16(3)：180—183
11. 郭元琦,陈丽仪,张洪来.分期整体针灸法一脑卒中偏瘫现代康复的新途径[J].现代康复,2001；5(3)：124-125
12. 刘悦,凌方明,章小平,等.分期针刺配合康复训练对急性脑卒中的早期康复….中国康复理论与实践,2002；8(11)：689-690
13. 东贵荣,张宣,李丹,等.头穴针刺治疗急性高血压性脑出血的临床对比研究[J].中国针灸,1994；14(3)：13
14. 赵大贵,穆敬平.头针结合促通技术对脑卒中偏瘫康复疗效的观察[J].中国针灸,2005；25(1)：19-21
15. 唐强,王德生.头针结合易化技术对脑卒中患者运动功能的影响[J].中国康复理论与实践,2001；7(2)：71-72
16. 陈英尧针刺治疗颅脑外伤后综合征65例. 云南中医杂志,1986(1)：281
17. 李涛,赵建国等.针刺对高血压脑出血术后病人神经功能的影响[J].中国针灸,2006；26(4)：247—249
18. 张树源,鲍春玲,东贵荣.头穴透刺治疗急性高血压性脑出血神经功能缺损的临床研究[J].针灸临床杂志,2005；21(3)：12
19. 韩守壮,李超.针灸治疗脑出血功能缺损恢复期68例疗效观察[J].河北中医,2005；27(2)：118-119
20. 陈汉红,汪继华.头针治疗脑出血术后后遗症48例疗效观察[J].华夏医学,2007；20(1)：113-114
21. 张中华,张彦通.头体针电交替治疗急性脑出血20例[J].中国中医急症,2008；17(
22. 黄宁,陈治林等.针灸治疗急性脑出血110例临床研究[J].江 西中医药,2006；9(37)：50—51
23. 张琳瑛,黄慧玲,只达石,王立波.激光多普勒连续监测脑创伤大鼠脑血流及针刺治疗的影响.天津医药2002,30(8)：483-485.
24. 聂卉.电缇针对中风偏瘫患者体感诱发电位动态观察[J].中国针灸,1999；19(6)：369-370.
25. 左芳,石现,田嘉禾,等.针刺头穴对运动条件下人脑功能成像的影响[J].中国针灸,2003；23(4)：231-233.
26. 周爽,徐佳,黄建华,等.电针对大鼠高血压性脑出血血肿周围组织NK-KB、TNF-a表达的影啊[J].中医药学刊,2005；23(6).985-986.
27. 江克文,张瑛,水泉祥电针预处理对新生大鼠缺氧缺血性脑损伤保护作用的可能机制[J]中国中西医结合杂志,2003,23(12)：914-916
28. 田菲,李平,等.醒脑开窍针法对脑缺血一再灌注家兔脑水肿、自由基的影响和相关分析[J].天津中医,
29. 王文远,赵建明,齐迎春.平衡针灸对局灶性脑缺血大鼠血清TNF-d, sIcAM-1的影响.临床军医杂志,2004,32(1)：5～7
30. 王文远.平衡针灸最新理论研究.中国中医药现代远程教育,2005,12(12)： 18～20
31. 刘汉平.针刺对家兔脑出血急性期脑组织SOD、LPO的影响[J].陕西中医,2003；24(6)：567—568
32. 田青,马骏等.电针对脑出血急性期脑组织含水量及SOD水平的影响[J].上海针灸杂志,2002；4(21)：36—38
33. 李研.针刺结合西药治疗脑出血急性期临床研究….北京中医,2005： 24(2)： 107-108.
34. 丁为国,李丽欣,许红,等.针刺百会穴对急性脑血肿大鼠局部脑血流量的影响[J].上海针灸杂志,2003；22(5)：7.
35. 邹伟,史榕荇,于学平.针刺对急性高血压脑出血大鼠HSP70mRNA的表达的调整作用[J].中医药学报,2003；31(1)：46-47
36. 纪晓军,何宏,温兆霞等.头穴针刺对大鼠急性脑出血血脑屏障影响的实验研究[J].中国急救医学,2001；21(11)：624-625.
37.邹伟,王茉蕾,等.针刺对急性高血压脑出血大鼠血浆ET和CGRP的调整作用[J].针灸临床杂志,2003；19(2)：50-51
38. 鲍春龄等.头穴透刺对急性高血压性脑出血患者血浆ET、CGRP的影响[J]中国针灸,2005；25(10)：717—719
[1]李志刚,耿昊,苑晓晨,魏开华.督脉电针对急性脊髓损伤6h后大鼠差异蛋白质组学的机理研究.北京中医药大学学报.2008,31(3)：202～205
[2]李志刚,付平,刘书坤,刘如春,耿昊,张春燕.针刺对急性脊髓损伤大鼠保护作用的机理研究.中国中医基础医学杂志.2005,11(11)：856～858
[3]李志刚,张春燕,刘如春,耿直.电针对急性脊髓损伤大鼠差异表达基因及钙离子作用的实验研究.北京中医药大学学报.待发表
[4].尹延庆,陈兵.创伤性脑损伤模型的研究进展.广东医学院学报,2008,12,26(6)：648-651.
[5].王帅,王东岩,曹东辉.大鼠自由落体脑外伤模型的应用及其针刺治疗的研究进展.中医药信息,2008,25(2)：49-51.
[6]OH SH, LEE J G, NA S J,I,etal. Prediction of earlyclinical severity and extent of neuronal damage in anterior circulation in farction using the initial serum neuron-specific enolase level[J].Arch neurol,2003,60(1):37-41
[7]TerrierB,Degand N,Guilpain P,etal Alpha-enolase a target of antibodies in infectious and autoimmune diseases [J]. Autoimmun Rev,2007,6(3):176-182
[8]Pereonti G,FerroA, AmatoF, etal, The Kelch protein NS1-BP interacts withalpha-enolase/MBP-landisinvolvedinc-mycgenetranscriptionalcontr ol [J].Biochim BiophysActa,2007,1773(12):1774-1785
[9]Guohua XI, Richard F, Hofyr.脑出血后脑水肿的形成机制(J].脑血管疾病杂志,2001；1(2)：99·106.
[10]Levy YS, Merms D, Panet H, et al. Induction of neuron · specific enolase promoter and neuronal markers in diferentiated mouse bone marrows stromal cells[J]. J Mol Neurosci,2003; 21(2):121-32.
[11]WoertgenC,RothoerlRD, BrawanskiA. Neuron-specificenolaseumlevelsa ftercontrolledcorticalimpact injuryintherat[J]. JNrotrauma,2001,18(5) :569-573.
[12]李宁,沈健康,徐福林,等. S-100B,NSE和MBP评估重型颅脑损伤预后的研究. 中国临床神经外科杂志,2004,9(2)：110.
[13]HerrmannM, JostS, KutzS, eta. 1Temporalprofileofreleaseofneuro-bioc hemicalmarkersofbraindamageaftertraumaticbraininjuryisassociatedwit hintracranialpathologyasdemonstratedincranialcomputerizedtomography [J]. JNeurotrauma,2000,17(2):113-122.
[14]RoydsJA,TimperleyWR, TaylorCB. Levelsofenolaseandotherzymesinthec erebrospinalfluidasindicesofpathologicalcha[J]. JNeurolNeurosurgPsyc hiatry,1981,44(8):1129-1135.
[15]RabinowicAL,CorrealeJD, BrachtKA, eta. 1Neuronspecificenolaseisinc reasedafternonconvulsivestate[J].Epilepsia,1995,36(2):475-476.
[16]ScheaarschmioltH,PrangeHW, ReibevH. Neuronspecificconcentrationin bloodasaprognosticparameterincerebrovasculardiseases[J]. Stroke,1994 ,25(3):558-559.
[17]童道明,廖杰芳.昏迷的诊断与处理,北京：人民军医出版社,1992,204-225.
[18]SingleB,LeistM,NicoteraP.Simultaneousreleaseofadenylatekinasean dcytochromecincelldeath. CellDeathDiffer,1998,5:1001-1003
[19]KohlerC, GahmA, NomaT, etal. Releaseofadenylatekinasefromthemitocho ndrialintermembranespaceduringapoptosis. FEBSLett,1999,447(1):10-12
[20]Lieber RL, Thornell LE, Friden JU. Muscle cytoskeletal disruption occurswithin the first 15 min of cyclic eccentric contraction. J Appl Physiol 1996;80(1):278-284
[21]Barash IA, Peters D, Friden J, et al. Desmin cytoskeletal modificationsafter a bout of eccentric exercise in the rat. Am J Physiol Regul IntegrComp Physiol 2002;283(4):R958-R963
[22]Friden J, Lieber RL. Segmental muscle fiber lesions after repetitiveeccentric contractions. Cell Tissue Res 1998;293:165-171
[23]Lieber RL, Schmitz MC, Mishra DK, et al. Contractile and cellularremodeling in rabbit skeletal muscle after cylic eccentric contractions. JAppl Physiol 1994;77(4):1926-1934
[24]Peters D, Barash IA, Burdi M, et al. Asynchronous functional, cellular and transcptional changes afters a bout of eccentric exercise in the rat. J physiol (Lond) 2003;553(Pt 3):947-957
[25]Friden J, Lieber RL. Eccentric exercise-induced injuries to contractile and cytoskeletal muscle fibre components. Acta Physiol Scand 2001;171 (3):321-326
[26]Vater R, Cullen MJ, Harris JB. The fate of desmin and titin during thedegeneration and regeneration of the soles muscle of the rat. ActaNeuropathol 1992;84 (3):278-288
[27]Yu JG, Thornell LE. Desmin and actin alterations in human muscles affectedbydelayedonsetmusclesoreness:ahighresolutionimmunocytochemi cal study. Histochem Cell Biol 2002;118(2):171-179
[28]Yu JG, Malm C, Thornell LE. Eccentric contractions leading to DOMS do not cause loss of desmin nor fibre necrosis in human muscle. HistochemCell Biol 2002;118(1):29-34
[29]Feasson L, Stockholm D, Freyssenet D, et al. Molecular adaptations ofneuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J Physiol (Lond)2002;543 (Pt 1):297-306
[30]Yu JG, Furst DO, Thornell LE. The mode of myofibril remodeling inhuman skeletal muscle affected by DOMS induced byeccentriccontractions. Histochem Cell Biol 2003;119(5):383-393
[31]Lipton P, Ischenic cell death in brain neurons[J].Physiol Rev, 1999,79(4):1431-1568.
[32]RaghapathiR, ContiAC, Grahnn DI etalM ikl traumatic; brain injury induces apoptotic cell dealh in the cortex that is preceded by decrease in cellular Bcl-2 immunoreactivity[J]. Neuroscience 2002,110(4): 605-616
[33]Daniel PT. Dissecting the pathwaysto death[J]. Leukenia,2000, 14(12):2035-2044
[34]Poulaki V, Mitsiades CS McMnllan C, etal Human retinoblastema cells are resistant apoptosis induced by death receptors role of caspase-8 gene silencing[J]. InvestOphthalmoIV is Sci 2005,46(1): 358-366
[35]刘伟,李庆军.Caspase与细胞凋亡[J].新乡医学院报,2005,22(1)：67-70
[36]Zhang P, Abraham VS, Kraft KR. Hyperthermic preconditioning protects against spinal cord ischemic jinjury[J]. Ann Thorac Surg,2000,70 (5):1490-1495.
[37]Lee J E, Yenari M A, Sun G H, et al. Differential neuroprotection from human heat shock protein 70 overexpression in vitro and in vivo models of ischemia-like conditions[J]. Exp Neurol2001,170(1):129-139.
[38]Motoyoshi N, Sakurai M, Hayashi T, et al. Establishment of a local coolingmodel against spinalcord ischemiarepresenting prolonged induction of heat shock protein[J]. J Thorac Cardiovasc Surg, 2001,122(2):351-357.
[39]Ouyang Y B, Xu L J, Sun Y J, et al. Overexpression of inducibleheatshock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucosedeprivation stress[J]. Cell Stress Chaperones, 2006,11(2):180-186.
[40]Miller J, McLachlan A D, Klug A. Repetitive zinc-binding domains in the protein transcription factor Ⅲ A from Xenopus oocytes [J]. EMBO J,1985,4:1609-1614.
[41]Lee M S, Gippert G P, Soman K V, et al. Three-dimensional solution structure of a single zinc finger DNA-binding domain [J]. Science,1989,245:635-637.
[42]Hoovers J M, Mannens M, John R, et al. High-resolution localization of 69 potential human zinc finger protein genes:a number are clustered[J]. Genomics,1992,12(2):254.
[43]Quintana A, Giralt M, Rojas S, et al. Differential role of tumor necrosis factor receptors in mouse brain inflammatory re-sponses in cryolesion brain injury. J Neurosci Res,2005,82(5):701-716.
[44]Quintana A, Giralt M, Rojas S, et al. Differential role of tumor necrosis factor receptors in mouse brain inflammatory re-sponses in cryolesion brain injury. J Neurosci Res,2005,82(5):701-716.
[45]王春梅 黄晓峰等 分泌颗粒素Ⅱ和促肾上腺皮质激素在脑损伤大鼠垂体腺细胞共存神经解剖学杂志Dec.2000：16(4)337～340
[46]Abdel-Aleem S, St Louis J, Hughes G, et al. Metabolic changes in the normal and hypoxic neonatal myocardium. Ann N Y Acad Sci,1999, 874:254-26
[47]Tator C, Fehlings M. Review ofthe secondaryinjurytheory ofacutespinal cord trauma with emphasis on vascular mechanisms. J Neurosurg,1991.75:15 -26.
[48]ShcgoN,WaroT,YoshihikoUetal. Ischernic tolerance due to theinduction of FLSP70inaratis chemic recirculation model.Brain Res,1993,615:281-288.
[49]Wynn RM, Davie JR, Cox RP,et al Molecular chaperones heatshock proteins foldases and matchmakers[J]. J Lab Clin Med1994 124 (1):31?36.
[50]Hard FU, HayerHartl M. Molecularchaperones in the cytosol fromnascent chain to folded protein[J]. Science,2002, 295(5561):1852-1858
[51]AlexzanderAA, StuartKC HSP70 binds to the cell surface of monotyres and induces cytokine exp2ssion W Abstracts from the second International conference on heat-shock proteins in immune response,8-12 october2000 famingtoy CT USA[J]. Cell Stess Chaperone2000,5(4):373-397
[52]Ciocca DR,Clark GM,Tandon AK, etal.Heat shock protein70 hsp70 in patients with axillary lymph node-negative breast cancer prognostic implications.J Natl Cancer Inst,1993,85(7):570-574
[53]唐文渊,晏怡.颅脑损伤研究的几个研究问题[].创伤外科杂志,2006,8(5)：475-477.
[54]徐敏,王树滨等.热休克蛋白70在乳腺癌中的表达及其与预后的关系.实用肿瘤杂志,2004,19(2)：110-113
[55]Vandler Heiden MG, Chandel NS, Li XX, et al. Outer mitorchondrial membrane permeability can regulate coupled respiration and cell survival[J].Proc Natl Acad Sci CSA,2000,97(9):4666-4671.
[56]AoloBernardiMitochondrialtransportofcations:channels, exchangers , andpermeabilitytransitionPhysiologicalReviews,1999,79(4):1127-1155
[57]YagodaN,vonRechenbergM, ZaganjorE, etal. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels Nature,2007,447(7146):864
[58]ButlerAE,HuangA,RaoPN, etallHematopoieticstemcellsde-Rivedfromad ultdonorsarenotasourceofpancreaticbeta-cellsina-dultnondiabetichuma ns. Diabetes,2007,56(7):1810
[59]AndreaM, Cesura, EmmanuelPinard, RobertSchubeneletal. Thevoltage_de pendentanionchannelisthetargetforanewclass of inhibitorsofthemitochondrial permeability transition pore.Biol Chem,2003,278(50):49812-49818
[60]YoshimotoT,SiesjoBK. Posttreatmentwiththeimmunosuppressantcyclos porinAintransientfocalischemia.BrainRes,1999,839:283-291
[61]何建军,任予,乔广东,等.CK19检测乳腺癌前哨淋巴结微转移的价值[J].中国现代医学,2002,12(2)：16—18.
[62]Velden LAVD, Schaafsma HE, Mann ii JJ, et al. Cytokeratin expression in normal and(pro)malignant head and neck epithelia; all overview [J]. Head & Neck,1993,15:133
[63]XiaCQ,WangJ, ShenWC. Hypoglycemic effect of insulin transferring conjugate in streptozotocininduced diabeticrats. JPharmcolExp Ther 2000:295:594
[2]朱诚,江基尧. 中国颅脑创伤研究现状与展望. 中华神经外科杂志,1999；15：1-2.
[3]顾峻,顾红玉,陈玉英,等.MK-801对新生大鼠脑外伤后神经元凋亡的影响.解剖学杂志,2006；29：738-740.
[4]周伟缺氧缺血性脑损伤的分子生物学研究进展[J]国外医学·儿科学分册,1998,25(1)：33-35
[5]谭来勋,孙圣刚.大鼠脑外伤灶周突触和星形胶质细胞的变化及对GM1的反应.中国综合临床,2006；22：875-877.
[6]Oyesiku NM, Evans CO, Houston S,etaL.Regional changes in the expression of neurotrophic factors and their receptors following acute traumatic brain injury in the adult rat brain 1999, 833(2):161-172.
[7]Zou Huang LL, Hayes RLet al. Liposome - mediated NGF gene transfection following neuronal injury;potential therapeutic applications. Gene Ther,1999,6 (6):994-1005.
[8]王向东,张建生.急性颅脑损伤患者血清TGF2B1, TNF-α水平变化及意义[J].山东医药,2006,46(30)：8-10.
[9]Chen Y, Constantini s, Trembovler V, etal. An experimental model of closed head injury in mice pathpphysiology, histothology,and cognition deficits [J]. J Neurotmma,1996,13(10):557 - 568.
[10]费舟,易声禹.章翱,等重型颅呐损伤后钙调素与自由基水平变化及尼莫地平和脑活素的作用中华创伤杂志,1994；10(4)275-280
[11]Newcomb J. K, Zhao X, et al. Temporal profile of apoptosis-like changes in neurons and astrocytes following controlled cortical impact injury in the rat Experimental Neurology,1999,158(1):76-88.
[12]Wong J, Hoe NW, Zhiwei F, etaL Apoptosis and traumatic brain injury. Neurocrit Cat,2005,3(2):177-182.
[13]朱诚.中国颅脑创伤研究现状与展望[].中华神经外科杂志,1999,15(1)：1
[14]江基尧,朱诚.现代颅脑损伤学[].上海：第二军医大学出版社,1999.113-145
[15]贺晓生,易声禹,章翔,等,脑弥漫性轴索损伤轴索内钙超载及钙拮抗剂的治疗作用[J]中华神经外科杂志,2000,16(1)：482521
[16]Joly LM, Mueignat V, Mariani J. Plotk in the rat brain[J J. Ceteb Blood Flow Metab,2004,24:124-131
[17]Lei BF, TanJ, CaiHW. Etc of. effect of moderate hypotheromia liqid percuidation in brain tissue after cardiac arrest and resuscitation Stroke.1994,25(1):147 - 151
[18]陈锡群,龚孝淑,江基尧等,低温对实验型颅脑损伤大鼠免疫功能的影响[J]中华神经外科杂志,2001,17(3)：168-170.
[19]江基尧,朱诚.颅脑创伤临床救治指南[M].上海：第二军医大学出版社,2002：158-159
[20]池京洋,只达石,黄楹,等.亚低温治疗对重型颅脑损伤患者血中神经元特异性烯醇化酶的影响及其临床意义.中国急救医学,2006；26：659-660.
[21]李昊,郑珊,施伟.亚低温对幼猪外伤性脑损伤保护作用的研究中华小儿外科杂志,2006；27：424-427.
[22]王光伟,刘运生,赵林,等.亚低温对大鼠脑损伤后脑组织炎性反应的影响.中华创伤杂志,2005；21：443-446.
[1]Werner T. Promoters can contribute to the elucidation of protein function. Trends Biotechnaol,2003,21(1):9-13
[2]王伟,谢杰,方坚.督脉电针治疗脊髓损伤的研究进展.针灸临床杂志,2005,21(1)：60-62
[3]Dudrick SJ, Wilmore DW, Vars H, et al. Long time total parenteral nutrition with growth in puppies and positive nitrogen balance in patients [J]. Surgical Forum,1967,18:356-359.
[4]孙言伟,姜颖,贺福初.差异蛋白质组学的研究进展[J].生命科学,2005,17(2)：137-140.
[5]纪建国,茹炳根.蛋白质组学研究相关技术及其在生物医学研究中的应用[J].药物生物科技,2002,9(1)：121
[6]Steinberg TH, Haugland RP, Singer VL. App lications of SY2 PRO o range and SYPRO red p ro tein gel stains [J]. Anal Biochem.1996, 1; 239 (2):238-245
[7]FountoulakisM. Application of proteomics technologies inthe investigation of the brain. Mass Spectrom Rev,20023:231-258
[8]Kim SI, VosholH, vanOostrum J, et a.1 Neuroproteomics: expression profiling of the brain's proteomes in health anddisease. Neurochem Res,2004,29:1317-1331
[9]Conti A, Sanchez Ruiz Y, Bachi A, etal. Proteome study of humancerebrospinal fluid following traumatic brain injury indicates fibrin(ogen)degralation products as trauma-associated markers [J]. J Neurotrauma,2004.21(7):854-863.
[10]J Jenkins Lw, Pete-GW, Dixon CE, et 81. Conventional and functionalproteomics using large format two-dimensional gel electrophoresis 24 hoursafter controlled oorfieal impact in postnatal day 17 rats[J]. J Neurotrauma,2002,19(6):715-740.
1.丁晶闭合性颅脑损伤术后针刺治疗的疗效对比观察中国针灸,1996,11：11
2.杨晓燕.针刺治疗脑出血60例临床观察[J].天津中医药,2005；22(4)： 286.
3.雷磊.针刺治疗闭合性颅脑损伤52例临床观察中国针灸,1997,3：1731
4.张卓,等.针灸推拿配合开颅血肿清除术治疗高血压性脑出血偏瘫 后遗症48例[J].辽宁中医杂志,2006；33(11)：1487
5. Counsel 1C. Boonykamkul S, Dennisi, et al. Primary in cerebralhae morrhage in the Oxfordshir communi ty Stroke prOjeet: prognosi S[J]. Cerebmvasc OiS,1995; 5(1):262-271
6.靳淼,侯文静.针刺治疗高血压性脑出血早期96例[J].山东中医杂志,2002,21(6)：347
7.东贵荣.头穴针刺对急性脑出血大鼠痛反应神经元电活动的双向调节.中国临床康复.2006,10(20)48-50.
8.吴逊.第二次全国脑电图与临床神经生理学术会议论文综述[J].脑电图学与神经精神疾病杂志,1990,6(2)：95
9.东贵荣.急性脑出血病人运动诱发电位的临床研究[C].第五届全国肌电图及诱发电位学术会议论文集,北京：1993
10. 钟长明,林洪茂,刘庆芳,等.针刺与肌张力平衡促通法对中风偏瘫患者早期康复的作用[J].中国康复医学杂志,2001；16(3)：180—183
11. 郭元琦,陈丽仪,张洪来.分期整体针灸法一脑卒中偏瘫现代康复的新途径[J].现代康复,2001；5(3)：124-125
12. 刘悦,凌方明,章小平,等.分期针刺配合康复训练对急性脑卒中的早期康复….中国康复理论与实践,2002；8(11)：689-690
13. 东贵荣,张宣,李丹,等.头穴针刺治疗急性高血压性脑出血的临床对比研究[J].中国针灸,1994；14(3)：13
14. 赵大贵,穆敬平.头针结合促通技术对脑卒中偏瘫康复疗效的观察[J].中国针灸,2005；25(1)：19-21
15. 唐强,王德生.头针结合易化技术对脑卒中患者运动功能的影响[J].中国康复理论与实践,2001；7(2)：71-72
16. 陈英尧针刺治疗颅脑外伤后综合征65例. 云南中医杂志,1986(1)：281
17. 李涛,赵建国等.针刺对高血压脑出血术后病人神经功能的影响[J].中国针灸,2006；26(4)：247—249
18. 张树源,鲍春玲,东贵荣.头穴透刺治疗急性高血压性脑出血神经功能缺损的临床研究[J].针灸临床杂志,2005；21(3)：12
19. 韩守壮,李超.针灸治疗脑出血功能缺损恢复期68例疗效观察[J].河北中医,2005；27(2)：118-119
20. 陈汉红,汪继华.头针治疗脑出血术后后遗症48例疗效观察[J].华夏医学,2007；20(1)：113-114
21. 张中华,张彦通.头体针电交替治疗急性脑出血20例[J].中国中医急症,2008；17(
22. 黄宁,陈治林等.针灸治疗急性脑出血110例临床研究[J].江 西中医药,2006；9(37)：50—51
23. 张琳瑛,黄慧玲,只达石,王立波.激光多普勒连续监测脑创伤大鼠脑血流及针刺治疗的影响.天津医药2002,30(8)：483-485.
24. 聂卉.电缇针对中风偏瘫患者体感诱发电位动态观察[J].中国针灸,1999；19(6)：369-370.
25. 左芳,石现,田嘉禾,等.针刺头穴对运动条件下人脑功能成像的影响[J].中国针灸,2003；23(4)：231-233.
26. 周爽,徐佳,黄建华,等.电针对大鼠高血压性脑出血血肿周围组织NK-KB、TNF-a表达的影啊[J].中医药学刊,2005；23(6).985-986.
27. 江克文,张瑛,水泉祥电针预处理对新生大鼠缺氧缺血性脑损伤保护作用的可能机制[J]中国中西医结合杂志,2003,23(12)：914-916
28. 田菲,李平,等.醒脑开窍针法对脑缺血一再灌注家兔脑水肿、自由基的影响和相关分析[J].天津中医,
29. 王文远,赵建明,齐迎春.平衡针灸对局灶性脑缺血大鼠血清TNF-d, sIcAM-1的影响.临床军医杂志,2004,32(1)：5～7
30. 王文远.平衡针灸最新理论研究.中国中医药现代远程教育,2005,12(12)： 18～20
31. 刘汉平.针刺对家兔脑出血急性期脑组织SOD、LPO的影响[J].陕西中医,2003；24(6)：567—568
32. 田青,马骏等.电针对脑出血急性期脑组织含水量及SOD水平的影响[J].上海针灸杂志,2002；4(21)：36—38
33. 李研.针刺结合西药治疗脑出血急性期临床研究….北京中医,2005： 24(2)： 107-108.
34. 丁为国,李丽欣,许红,等.针刺百会穴对急性脑血肿大鼠局部脑血流量的影响[J].上海针灸杂志,2003；22(5)：7.
35. 邹伟,史榕荇,于学平.针刺对急性高血压脑出血大鼠HSP70mRNA的表达的调整作用[J].中医药学报,2003；31(1)：46-47
36. 纪晓军,何宏,温兆霞等.头穴针刺对大鼠急性脑出血血脑屏障影响的实验研究[J].中国急救医学,2001；21(11)：624-625.
37.邹伟,王茉蕾,等.针刺对急性高血压脑出血大鼠血浆ET和CGRP的调整作用[J].针灸临床杂志,2003；19(2)：50-51
38. 鲍春龄等.头穴透刺对急性高血压性脑出血患者血浆ET、CGRP的影响[J]中国针灸,2005；25(10)：717—719
[1]李志刚,耿昊,苑晓晨,魏开华.督脉电针对急性脊髓损伤6h后大鼠差异蛋白质组学的机理研究.北京中医药大学学报.2008,31(3)：202～205
[2]李志刚,付平,刘书坤,刘如春,耿昊,张春燕.针刺对急性脊髓损伤大鼠保护作用的机理研究.中国中医基础医学杂志.2005,11(11)：856～858
[3]李志刚,张春燕,刘如春,耿直.电针对急性脊髓损伤大鼠差异表达基因及钙离子作用的实验研究.北京中医药大学学报.待发表
[4].尹延庆,陈兵.创伤性脑损伤模型的研究进展.广东医学院学报,2008,12,26(6)：648-651.
[5].王帅,王东岩,曹东辉.大鼠自由落体脑外伤模型的应用及其针刺治疗的研究进展.中医药信息,2008,25(2)：49-51.
[6]OH SH, LEE J G, NA S J,I,etal. Prediction of earlyclinical severity and extent of neuronal damage in anterior circulation in farction using the initial serum neuron-specific enolase level[J].Arch neurol,2003,60(1):37-41
[7]TerrierB,Degand N,Guilpain P,etal Alpha-enolase a target of antibodies in infectious and autoimmune diseases [J]. Autoimmun Rev,2007,6(3):176-182
[8]Pereonti G,FerroA, AmatoF, etal, The Kelch protein NS1-BP interacts withalpha-enolase/MBP-landisinvolvedinc-mycgenetranscriptionalcontr ol [J].Biochim BiophysActa,2007,1773(12):1774-1785
[9]Guohua XI, Richard F, Hofyr.脑出血后脑水肿的形成机制(J].脑血管疾病杂志,2001；1(2)：99·106.
[10]Levy YS, Merms D, Panet H, et al. Induction of neuron · specific enolase promoter and neuronal markers in diferentiated mouse bone marrows stromal cells[J]. J Mol Neurosci,2003; 21(2):121-32.
[11]WoertgenC,RothoerlRD, BrawanskiA. Neuron-specificenolaseumlevelsa ftercontrolledcorticalimpact injuryintherat[J]. JNrotrauma,2001,18(5) :569-573.
[12]李宁,沈健康,徐福林,等. S-100B,NSE和MBP评估重型颅脑损伤预后的研究. 中国临床神经外科杂志,2004,9(2)：110.
[13]HerrmannM, JostS, KutzS, eta. 1Temporalprofileofreleaseofneuro-bioc hemicalmarkersofbraindamageaftertraumaticbraininjuryisassociatedwit hintracranialpathologyasdemonstratedincranialcomputerizedtomography [J]. JNeurotrauma,2000,17(2):113-122.
[14]RoydsJA,TimperleyWR, TaylorCB. Levelsofenolaseandotherzymesinthec erebrospinalfluidasindicesofpathologicalcha[J]. JNeurolNeurosurgPsyc hiatry,1981,44(8):1129-1135.
[15]RabinowicAL,CorrealeJD, BrachtKA, eta. 1Neuronspecificenolaseisinc reasedafternonconvulsivestate[J].Epilepsia,1995,36(2):475-476.
[16]ScheaarschmioltH,PrangeHW, ReibevH. Neuronspecificconcentrationin bloodasaprognosticparameterincerebrovasculardiseases[J]. Stroke,1994 ,25(3):558-559.
[17]童道明,廖杰芳.昏迷的诊断与处理,北京：人民军医出版社,1992,204-225.
[18]SingleB,LeistM,NicoteraP.Simultaneousreleaseofadenylatekinasean dcytochromecincelldeath. CellDeathDiffer,1998,5:1001-1003
[19]KohlerC, GahmA, NomaT, etal. Releaseofadenylatekinasefromthemitocho ndrialintermembranespaceduringapoptosis. FEBSLett,1999,447(1):10-12
[20]Lieber RL, Thornell LE, Friden JU. Muscle cytoskeletal disruption occurswithin the first 15 min of cyclic eccentric contraction. J Appl Physiol 1996;80(1):278-284
[21]Barash IA, Peters D, Friden J, et al. Desmin cytoskeletal modificationsafter a bout of eccentric exercise in the rat. Am J Physiol Regul IntegrComp Physiol 2002;283(4):R958-R963
[22]Friden J, Lieber RL. Segmental muscle fiber lesions after repetitiveeccentric contractions. Cell Tissue Res 1998;293:165-171
[23]Lieber RL, Schmitz MC, Mishra DK, et al. Contractile and cellularremodeling in rabbit skeletal muscle after cylic eccentric contractions. JAppl Physiol 1994;77(4):1926-1934
[24]Peters D, Barash IA, Burdi M, et al. Asynchronous functional, cellular and transcptional changes afters a bout of eccentric exercise in the rat. J physiol (Lond) 2003;553(Pt 3):947-957
[25]Friden J, Lieber RL. Eccentric exercise-induced injuries to contractile and cytoskeletal muscle fibre components. Acta Physiol Scand 2001;171 (3):321-326
[26]Vater R, Cullen MJ, Harris JB. The fate of desmin and titin during thedegeneration and regeneration of the soles muscle of the rat. ActaNeuropathol 1992;84 (3):278-288
[27]Yu JG, Thornell LE. Desmin and actin alterations in human muscles affectedbydelayedonsetmusclesoreness:ahighresolutionimmunocytochemi cal study. Histochem Cell Biol 2002;118(2):171-179
[28]Yu JG, Malm C, Thornell LE. Eccentric contractions leading to DOMS do not cause loss of desmin nor fibre necrosis in human muscle. HistochemCell Biol 2002;118(1):29-34
[29]Feasson L, Stockholm D, Freyssenet D, et al. Molecular adaptations ofneuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J Physiol (Lond)2002;543 (Pt 1):297-306
[30]Yu JG, Furst DO, Thornell LE. The mode of myofibril remodeling inhuman skeletal muscle affected by DOMS induced byeccentriccontractions. Histochem Cell Biol 2003;119(5):383-393
[31]Lipton P, Ischenic cell death in brain neurons[J].Physiol Rev, 1999,79(4):1431-1568.
[32]RaghapathiR, ContiAC, Grahnn DI etalM ikl traumatic; brain injury induces apoptotic cell dealh in the cortex that is preceded by decrease in cellular Bcl-2 immunoreactivity[J]. Neuroscience 2002,110(4): 605-616
[33]Daniel PT. Dissecting the pathwaysto death[J]. Leukenia,2000, 14(12):2035-2044
[34]Poulaki V, Mitsiades CS McMnllan C, etal Human retinoblastema cells are resistant apoptosis induced by death receptors role of caspase-8 gene silencing[J]. InvestOphthalmoIV is Sci 2005,46(1): 358-366
[35]刘伟,李庆军.Caspase与细胞凋亡[J].新乡医学院报,2005,22(1)：67-70
[36]Zhang P, Abraham VS, Kraft KR. Hyperthermic preconditioning protects against spinal cord ischemic jinjury[J]. Ann Thorac Surg,2000,70 (5):1490-1495.
[37]Lee J E, Yenari M A, Sun G H, et al. Differential neuroprotection from human heat shock protein 70 overexpression in vitro and in vivo models of ischemia-like conditions[J]. Exp Neurol2001,170(1):129-139.
[38]Motoyoshi N, Sakurai M, Hayashi T, et al. Establishment of a local coolingmodel against spinalcord ischemiarepresenting prolonged induction of heat shock protein[J]. J Thorac Cardiovasc Surg, 2001,122(2):351-357.
[39]Ouyang Y B, Xu L J, Sun Y J, et al. Overexpression of inducibleheatshock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucosedeprivation stress[J]. Cell Stress Chaperones, 2006,11(2):180-186.
[40]Miller J, McLachlan A D, Klug A. Repetitive zinc-binding domains in the protein transcription factor Ⅲ A from Xenopus oocytes [J]. EMBO J,1985,4:1609-1614.
[41]Lee M S, Gippert G P, Soman K V, et al. Three-dimensional solution structure of a single zinc finger DNA-binding domain [J]. Science,1989,245:635-637.
[42]Hoovers J M, Mannens M, John R, et al. High-resolution localization of 69 potential human zinc finger protein genes:a number are clustered[J]. Genomics,1992,12(2):254.
[43]Quintana A, Giralt M, Rojas S, et al. Differential role of tumor necrosis factor receptors in mouse brain inflammatory re-sponses in cryolesion brain injury. J Neurosci Res,2005,82(5):701-716.
[44]Quintana A, Giralt M, Rojas S, et al. Differential role of tumor necrosis factor receptors in mouse brain inflammatory re-sponses in cryolesion brain injury. J Neurosci Res,2005,82(5):701-716.
[45]王春梅 黄晓峰等 分泌颗粒素Ⅱ和促肾上腺皮质激素在脑损伤大鼠垂体腺细胞共存神经解剖学杂志Dec.2000：16(4)337～340
[46]Abdel-Aleem S, St Louis J, Hughes G, et al. Metabolic changes in the normal and hypoxic neonatal myocardium. Ann N Y Acad Sci,1999, 874:254-26
[47]Tator C, Fehlings M. Review ofthe secondaryinjurytheory ofacutespinal cord trauma with emphasis on vascular mechanisms. J Neurosurg,1991.75:15 -26.
[48]ShcgoN,WaroT,YoshihikoUetal. Ischernic tolerance due to theinduction of FLSP70inaratis chemic recirculation model.Brain Res,1993,615:281-288.
[49]Wynn RM, Davie JR, Cox RP,et al Molecular chaperones heatshock proteins foldases and matchmakers[J]. J Lab Clin Med1994 124 (1):31?36.
[50]Hard FU, HayerHartl M. Molecularchaperones in the cytosol fromnascent chain to folded protein[J]. Science,2002, 295(5561):1852-1858
[51]AlexzanderAA, StuartKC HSP70 binds to the cell surface of monotyres and induces cytokine exp2ssion W Abstracts from the second International conference on heat-shock proteins in immune response,8-12 october2000 famingtoy CT USA[J]. Cell Stess Chaperone2000,5(4):373-397
[52]Ciocca DR,Clark GM,Tandon AK, etal.Heat shock protein70 hsp70 in patients with axillary lymph node-negative breast cancer prognostic implications.J Natl Cancer Inst,1993,85(7):570-574
[53]唐文渊,晏怡.颅脑损伤研究的几个研究问题[].创伤外科杂志,2006,8(5)：475-477.
[54]徐敏,王树滨等.热休克蛋白70在乳腺癌中的表达及其与预后的关系.实用肿瘤杂志,2004,19(2)：110-113
[55]Vandler Heiden MG, Chandel NS, Li XX, et al. Outer mitorchondrial membrane permeability can regulate coupled respiration and cell survival[J].Proc Natl Acad Sci CSA,2000,97(9):4666-4671.
[56]AoloBernardiMitochondrialtransportofcations:channels, exchangers , andpermeabilitytransitionPhysiologicalReviews,1999,79(4):1127-1155
[57]YagodaN,vonRechenbergM, ZaganjorE, etal. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels Nature,2007,447(7146):864
[58]ButlerAE,HuangA,RaoPN, etallHematopoieticstemcellsde-Rivedfromad ultdonorsarenotasourceofpancreaticbeta-cellsina-dultnondiabetichuma ns. Diabetes,2007,56(7):1810
[59]AndreaM, Cesura, EmmanuelPinard, RobertSchubeneletal. Thevoltage_de pendentanionchannelisthetargetforanewclass of inhibitorsofthemitochondrial permeability transition pore.Biol Chem,2003,278(50):49812-49818
[60]YoshimotoT,SiesjoBK. Posttreatmentwiththeimmunosuppressantcyclos porinAintransientfocalischemia.BrainRes,1999,839:283-291
[61]何建军,任予,乔广东,等.CK19检测乳腺癌前哨淋巴结微转移的价值[J].中国现代医学,2002,12(2)：16—18.
[62]Velden LAVD, Schaafsma HE, Mann ii JJ, et al. Cytokeratin expression in normal and(pro)malignant head and neck epithelia; all overview [J]. Head & Neck,1993,15:133
[63]XiaCQ,WangJ, ShenWC. Hypoglycemic effect of insulin transferring conjugate in streptozotocininduced diabeticrats. JPharmcolExp Ther 2000:295:594