鞘内注射rAAV/hPPE对慢性神经病理痛大鼠的镇痛作用  

Analgesic Effect of Intrathecal Injection of rAAV/hPPE in Rats with Chronic Neuropathic Pain

作　　者：江辉[1] 高峰[1] 田学愎[1] 徐颖[1] 王鹏[1] 田玉科[1] 杨辉[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉学教研室,武汉430030

出　　处：《华中科技大学学报（医学版）》2013年第4期401-404,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.80872440)

摘　　要：目的观察含人前脑啡肽原基因的腺相关病毒rAAV/hPPE转染后对慢性疼痛模型大鼠的镇痛作用。方法 48只SD大鼠随机分为3组:对照组(C组)、坐骨神经痛(CCI)+rAAV/hPPE注射组(SH组)和CCI+生理盐水注射组(SS组)。SS组和SH组大鼠先行右侧CCI术,1周后分别于蛛网膜下腔L4～L6段注射生理盐水或rAAV/hPPE 20μL。于CCI前至注射后8周内测量大鼠患侧机械痛阈和热痛阈值,并于注射8周后处死大鼠取下段脊髓组织(L4～L6段)行免疫组织化学和放射免疫荧光方法检测亮氨酸脑啡肽(L-EK)的表达及含量。结果 CCI模型建立1周后,SS组和SH组大鼠机械痛阈和热痛阈明显下降(均P<0.01),注射rAAV/hPPE或生理盐水后,SH组大鼠痛阈呈明显上升趋势,而SS组大鼠没有观察到相似现象。注射8周后大鼠下段脊髓组织中L-EK含量,SH组比C组和SS组显著增高。结论 rAAV/hPPE注射能将hPPE整合到宿主神经细胞,从而显著抑制慢性疼痛模型大鼠的痛觉过敏。Objective To observe the analgesic effect of intrathecal injection of recombinant adeno-associated virus vector with human preproenkephalin gene（rAAV/hPPE）on chronic neuropathic pain in rats.Methods A total of 48adult male Sprague-Dawley rats were randomly divided into three groups（n=16each）：control group,chronic constriction injury（CCI）＋ saline injection group（SS group）and CCI＋rAAV/hPPE injection group（SH group）.Saline or rAAV/hPPE（20μL）was injected into the lumbar subarachnoid space（L4—L6）near the spinal cord 1week after right-side CCI in the SS and SH groups,respectively.Bilateral paw withdrawal mechanical threshold（PWMT）and paw withdrawal thermal latency（PWTL）were detected each day 1week before injection to 8weeks after injection.The content of L-EK in the spinal cord of L4—L6was determined by using immunohistochemistry and radioimmunoassay 8weeks after injection.Results Allodynia-like behavior was observed in rats 1week following CCI.As compared with control group,the PWMT was significantly decreased（P0.01）and the PWTL significantly shortened（P0.01）in both SH and SS groups at 1week.The PWMT was markedly increased in the SH group after rAAV/hPPE injection（P0.01）,but similar phenomenon was not found in the SS group.The content of L-EK in the lumbar spinal cord in the SH group was significantly higher than that in the control group and SS group 8weeks after injection（P0.01）.Conclusion Intrathecal injection of rAAV/hPPE can alleviate the allodynia-like behavior in chronic neuropathic pain rats,which is associated with rAAV-mediated integration of hPPE gene into host cells.

关 键 词：腺相关病毒 脑啡肽 镇痛 

分 类 号：R971[医药卫生—药品]