| | | | | 他克莫司对大鼠急性脊髓损伤后细胞凋亡及热休克蛋白70表达的影响 | | | 潘峰;陈安民;郭风劲;祝成亮 | | | 目的探讨脊髓损伤后他克莫司(FK506)对热休克蛋白70表达的影响及其与神经细胞凋亡的关系。方法采用Allen法建立大鼠急性脊髓损伤模型。雄性Wistar大鼠72只,随机分为假手术组(n=12)、损伤组(n=30)和FK506组(n=30)。FK506组伤后5min一次性经尾静脉注射FK506(0.3mg/kg),假手术组和损伤组以相同方法给予0.9%的生理盐水。术后行脊髓功能评分;逆转录聚合酶链反应(RT-PCR)检测热休克蛋白70mRNA的表达;免疫组织化学染色检测半胱氨酸天冬氨酸蛋白酶-3和热休克蛋白70的表达;原位末端标记法(TUNEL)检测神经细胞凋亡。结果热休克蛋白70mRNA和蛋白的表达在FK506组较损伤组明显增加(P<0.05),分别于伤后6、24h达高峰;FK506组半胱氨酸天冬氨酸蛋白酶-3的表达和神经细胞凋亡均较损伤组明显减少(P<0.01,P<0.05);脊髓功能评分在FK506组显著优于损伤组(P<0.05)。结论FK506能抑制脊髓损伤后半胱氨酸天冬氨酸蛋白酶-3的活性,减轻神经细胞凋亡,促进脊髓功能恢复,其机制可能与诱导热休克蛋白70表达增加有关。
【作者单位】：武汉华中科技大学同济医学院附属同济医院骨科;武汉华中科技大学同济医学院附属同济医院骨科;武汉华中科技大学同济医学院附属同济医院骨科;武汉大学生命科学院
【关键词】：脊髓损伤;他克莫司;热休克蛋白70;半胱氨酸天冬氨酸蛋白酶-3
【分类号】：R651.2
【DOI】：CNKI:ISSN:0529-5815.0.2006-24-015
【正文快照】：
脊髓损伤(spinal cord injury,SCI)的机制包括由各种致伤因素造成的原发性损伤和随之而来的继发性损伤,而后者的结果往往更为严重,脊髓继发性损伤主要是因神经细胞凋亡[1]。近年来一种用于预防移植排斥反应的大环内酯类抗生素-他克莫司(FK506),在神经营养、保护方面的作用引起人们关注[2]。本实验旨在通过建立大鼠脊髓损伤模型来探讨FK506对脊髓损伤后热休克蛋白70(heatshock protein70,HSP70)和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)表达的影响及其与神经细胞凋亡的关系。材料与方法1.实验动物与分组:72只成年雄性健康Wistar大鼠(由武… | | |  推荐 CAJ下载  PDF下载 | | | CAJViewer7.0阅读器支持所有CNKI文件格式，AdobeReader仅支持PDF格式 | | | | Effect of tacrolimus on apoptosis and expression of heat shock protein 70 after acute spinal cord injury in rats | | | PAN Feng*;CHEN An-min;GUO Feng-jin;ZHU Cheng-liang.*Department of Orthopaedics;Tongji Hospital;Tongji Medical College;Huazhong University of Science and Technology;Wuhan 430030;China | | | Objective To investigate the effect of tacrolimus on expression of heat shock protein 70 (HSP 70) after spinal cord injuries (SCI) in rats and the relationship between expression of HSP 70 and apoptosis of neural cells.Methods Seventy-two male rats were divided randomly into three groups: the sham-operation group, the injury group and the group treated with tacrolimus, and the latter two groups were SCI with a weight-drop impactor at the T_ 10 vertebrae level (10 g weight was dropped from a 4.0 cm height). The tacrolimus group was injected with tacrolimus 5 minutes after SCI, while the other groups received 0.9% saline likewise. The inclined plate and BBB (Basso, Beattie and Bresnahan) scales were used to evaluate hindlimb neurological function. The expression of HSP 70 mRNA after SCI was detected by using reverse transcription polymerase chain reactions (RT-PCR) and immunohistochemistry staining was performed to determine the protein expression of HSP 70 and Caspase-3. The apoptosis of neural cells was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuredine triphosphate-digoxin nick end labeling (TUNEL) method.Results Compared with the injury group, the expression of HSP 70 was significantly higher in the tacrolimus group, and the peak expression of HSP 70 mRNA and protein was respectively observed at 6, 24 h after SCI.Caspase-3-positive or TUNEL-positive cells were significantly less in the tacrolimus group than in the injury group. Neurological function score of the tacrolimus group was significantly better than that of the injury group.Conclusions Tacrolimus may inhibit activity of Caspase-3, attenuate apoptosis of neural cells and ameliorate neurological function recovery after SCI by inducing high expression of HSP 70.
【Keyword】：Spinal cord injuries;Tacrolimus;Heat shock protein 70;Caspase-3 |
| | | | | | 1 | 蔡卫华,贾连顺,叶晓健,袁文,陈雄生,周许辉,宋滇文; 甲基强的松龙对脊髓损伤后伤段脊髓线粒体功能的影响 [J];中国脊柱脊髓杂志; 2005年12期 | | 2 | 王宏,闫慧博,廖华,邱小忠,鲁凯伍,江建明,余磊,赖桂华,王晓佳; 大剂量甲基强的松龙对大鼠急性损伤脊髓Nogo-A表达量影响的研究 [J];中国临床解剖学杂志; 2006年03期 | | 3 | 王刚,吴小涛,茅祖斌,祁亚斌,付文芹,赵梓汝; 米诺环素对大鼠脊髓损伤后线粒体细胞色素C的释放及神经细胞凋亡的影响 [J];中国脊柱脊髓杂志; 2006年07期 |
|
| | | | | | 1 | Kyung-Min Lee, Bong-Seok Kang, Hye-Lim Lee, Sun-Joo Son, Sung-Hun Hwang, Dong-Sun Kim, Jae-Sik Park and Hee-Jung Cho; Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity [M];European Journal of Neuroscience; 2004年 | | 2 | Hayashi Y, Shumsky JS, Connors T, et al; Immunosuppression with either cyclosporine a or FK506 supports survival of transplanted fibroblasts and pro- motes growth of host axons into the transplant after spinal cord injury [M];J Neuro- trauma; 2005年 | | 3 | Keswani SC,Rosenberg B,H oke A; The use of GAP-43m RNA quantification in high throughput screening of putative neuroprotective agents in dorsal root ganglion cultures[J] [M];J Neurosci M ethods; 2004年 | | 4 | Takahashi G, Sakurai M, Abe K, et al; MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits [M];J Thorac Cardiovasc Surg; 2003年 | | 5 | Takahashi G, Sakurai M, Abe K, et al; MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia [M];Ann Thorac Surg; 2004年 | | 6 | TENG Y D, CHOI H, ONARIO R C, et al; Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury [M];Proc Natl Acad Sci U S A; 2004年 | | 7 | Kaptanoglu E, Caner H, Solaroglu I,et al; Mexiletine treatment-induced in- hibition of caspase-3 activation and improvement of behavioral recovery after spinal cord injury [M];J Neurosurg Spine; 2005年 | | 8 | Lopez-Vales R,Garcia-Alias G,Fores J,et al; FK506reduces tissue dam age and prevents functional deficit after spinal cord injury in the rat[J] [M];J Neurosci Res; 2005年 | | 9 | Vitellaro-Zuccarello L, Mazzetti S, Madaschi I, et al; Erythropoietin-mediated preservation of the white matter in rat spinal cord injury [M];Neuroscience; 2007年 | | 10 | Hashizume K, Ueda T, Shimizu H, et al; Effect of the free radical scavenger MCI-186 on spinal cord reperfasion after transient ischemia in the rabbit [M];Jpn J Thorac Cardiovasc Surg; 2005年 |
|
| | | | | | 1 | 刘艳,刘高峰,王杨; 他克莫司在器官移植中的应用概述 [J];中国药师; 2003年03期; 47-49 | | 2 | 周逸鸣,崔尧元,吕迁洲; 脏器移植后应用他克莫司引起的高血压以及神经系统并发症 [J];中国临床药学杂志; 2003年02期; 46-49 | | 3 | 魏淑贞,张德奎,姜山,藏运金; 肝移植术后服用他克莫司致神经毒性反应的观察 [J];中国现代医学杂志; 2004年06期; 98-99 | | 4 | 韩磊,吴兴裕; 热休克蛋白70与缺血性脑损伤 [J];中华航空航天医学杂志; 2000年04期; 62 | | 5 | Toth C.C.,Burak K.,Becker W. ,陈云春; 西罗莫司替换他克莫司治疗肝移植患者成功消除其伴先兆偏头痛的复发 [J];世界核心医学期刊文摘.神经病学分册; 2005年08期; 39 | | 6 | 张子印,吕国蔚; 脊髓损伤模型与再生实验研究(综述) [J];中华神经外科杂志; 1991年02期; 72-74 | | 7 | 赵立，李涛，贾连顺; 机械性脊髓损伤模型的应用现状 [J];中华实验外科杂志; 1997年02期; 128-129 | | 8 | 周天健; 21世纪与我国脊髓损伤及其康复事业 [J];伤残医学杂志; 2005年03期; 58-62 | | 9 | 王佳; 脊髓损伤后的烧伤 [J];国外医学.物理医学与康复学分册; 1990年01期; 48 | | 10 | 李顺业; 脊髓损伤的某些问题 [J];国际神经病学神经外科学杂志; 1981年05期; 3-5 |
|
| | | | | | 1 | 侯春林,王诗波,张世民,钟贵彬,陈爱民,张伟,衷鸿宾,王金武,徐瑞生,刘明轩; 脊髓损伤后膀胱功能重建 [A];2005'中国修复重建外科论坛论文汇编 [C]; 2005年 | | 2 | 徐基民,纪树荣,张琦; 脊髓损伤后并发骨折的临床观察 [A];第六次全国运动疗法学术会议论文集 [C]; 2002年 | | 3 | 张树栋,马潞林,赵磊,王国良,侯小飞,罗康平; 胰肾联合移植受者他克莫司治疗窗浓度的初步探讨 [A];第十二届全国、第七届全球华人泌尿外科学术会议论文汇编（下册） [C]; 2005年 | | 4 | 侯春林,王诗波,张世民,钟贵彬,衷鸿宾,王金武,徐瑞生,刘明轩,陈爱民,张伟; 脊髓损伤后膀胱功能重建 [A];中华医学会第八届骨科学术会议暨第一届国际COA学术大会论文摘要集 [C]; 2006年 | | 5 | 汪琴; 脊髓损伤后疼痛与处置 [A];中国康复医学会第三次康复治疗学术大会论文汇编 [C]; 2002年 | | 6 | 任振唤; 他克莫司在肝移植后对糖代谢的影响和控制 [A];2004年浙江省检验医学学术会议论文汇编 [C]; 2004年 | | 7 | 张志杰; 脊髓损伤后肌痉挛的综合康复治疗 [A];第四届全国康复治疗学术大会论文摘要汇编 [C]; 2004年 | | 8 | 郭世绂,李少博,何铁春,李健民; 应用东茛菪硷观察脊髓损伤后诱发电位的变化 [A];跨世纪骨伤杰出人才科技成果荟萃 [C]; 2004年 | | 9 | 刘大立,张俊,李朝,蔡合金; 脊髓损伤后心理调适对整体康复的意义 [A];第五次全国创伤康复暨第七次全国运动疗法学术会议论文汇编 [C]; 2004年 | | 10 | 吴海燕,谢中光,张兰菊,李亚平,张立仁,陈佩兰,刘超英; 脊髓损伤后髓鞘的亚微病理 [A];中国细胞生物学学会第五次会议论文摘要汇编 [C]; 1992年 |
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