Rolipram对大鼠急性脊髓损伤的保护作用  

Study of Rolipram on the neuroprotection of acute spinal cord injury in rat

作　　者：祁全[1] 毕郑钢[1] 张磊[2] 吴滨奇[1] 潘尚哈[3] 朱江[1] 

机构地区：[1]哈尔滨医科大学附属第一医院骨科,哈尔滨市150001 [2]哈尔滨医科大学病理教研室 [3]哈尔滨医科大学附属第一医院中心实验室,哈尔滨市150001

出　　处：《中国脊柱脊髓杂志》2008年第10期766-770,I0002,共6页Chinese Journal of Spine and Spinal Cord

基　　金：黑龙江省青年基金资助项目(QC06C073);黑龙江省卫生厅基金资助项目(2006-078);黑龙江省教育厅基金资助项目(10551170);黑龙江省博士后资助项目;哈医大一院科研基金资助项目(2007037)

摘　　要：目的:研究磷酸二酯酶(IV)抑制剂Rolipram对大鼠急性脊髓损伤的保护机制。方法:健康Waster大鼠70只,Allen′s法(10g×2.5cm)打击制作脊髓损伤(SCI)模型。实验组伤后立即皮下注射Rolipram 2.5mg/kg/d,每天分2次注射,至第14天;对照组皮下注射与实验组相同剂量的生理盐水。分别通过HE染色,免疫组化,测定6h、24h、72h、7d、14d五个时间段病理变化及B细胞淋巴瘤-2基因(bcl-2)表达,TUNEL法测定24h～7d凋亡细胞水平,并用放免方法测定各组大鼠给药3h和6h后脊髓中环磷酸腺苷(cAMP)含量。结果:脊髓损伤后,对照组和实验组TUNEL阳性细胞在24h～7d均有表达,多数为胶质细胞;3～7d时实验组凋亡细胞较对照组明显减少(P<0.05)。脊髓损伤后3～14d,实验组bcl-2表达强于对照组(P<0.05);放免方法测定实验组(给药3h和6h时)脊髓cAMP明显高于对照组(P<0.05)。结论:磷酸二酯酶抑制剂Rolipram对大鼠急性脊髓损伤具有一定保护作用,这一作用可能通过多种途径,升高细胞内cAMP,进而上调bcl-2等保护性基因是其中之一。Objective：To study the neuroprotection of phosphodiesterase-4 inhibitor rolipram to the acute spinal cord injury of rats.Method：70 healthy Waster rats were used in the experiment .Spinal cord injury（SCl） was performed with Allen＇s method.The blank group only received laminectomy,Afler injury,rolipram（2.5mg/kg） were used twice every day by hypodermical injection in experiment group,and 16% DMSO was used in the control group.The cAMP levels of the spinal cord in the experiment group at 27h and 30h （3h and 6h after rolipram injection in the first day after SCI） and in blank group and control group at 27h were evaluated by RIA.The pathological changes of spinal cord were observed by HE and immunohistochemistry mathod （Bcl-2） at five time points （6h,24h,3d,7d,14d）.TUNEL staining was applied for observing apoptosis at 24h,3d,7d. Result：The pathological change under light microscope was similar in botth experiment group and control group,but the inflammatory cell infiltration was not markedly in the former.The cAMP level of the Spinal cord in the experiment group at 3-6 h after rolipram was applied and in blank group were higher than that in control group （P〈0.05）.The positive expression of bcl-2 in marginal zone of experirnent group was stronger than that of control group at 3d,7d,14d （P〈0.O5）.The positive expression of TUNEL existed at 24h-7d in control group and experiment group.The most cells of TUNEL staining were glial cells.Apoptosis at 3d ,7d in experiment group decreased obviously compared to the control group （P〈0.05）.The positive ceils of bcl-2 and TUNEL in the blank group were rare.Conclusion：Rolipram,which is phosphodiesterase-4 inhibitor,may have the protection to the rat spinal cord injury to some extent by several pathways.One of the possible pathways is the increasing of cAMP in cell and then up-regulating of bcl-2.

关 键 词：磷酸二酯酶(IV)抑制剂 脊髓损伤 环磷酸腺苷(cAMP) 细胞凋亡 B细胞淋巴瘤-2基因(bcl-2) 

分 类 号：R971[医药卫生—药品] R683.2[医药卫生—药学]