中文摘要：

目的观察鞘内注射人前脑啡肽原基因（HPPE）单纯疱疹病毒Ⅰ型（HSV-Ⅰ）扩增子载体对神经病理性疼痛大鼠的镇痛作用。方法60只成年雄性SD大鼠，体重260～320g，鞘内置管成功3d后，建立坐骨神经结扎致神经痛（CCI）模型，随机分为以下4组（n=15）：假手术组＋生理盐水（Sham组），Sham组仅暴露右侧坐骨神经分支；CCI＋生理盐水（NS组）；CCI＋pHSVIRES-LacZ空白载体组（SHZ组）；CCI＋pHSVIRES-HPPE-LacZ载体组（SHPZ组）。将构建好的含HPPE的重组HSV-Ⅰ扩增子载体注入大鼠鞘内，1周后从NS组、SHZ组和SHPZ组中各抽出9只大鼠用于X-gal染色原位检测LacZ的表达，RT-PCR方法检测HPPE的表达，放免法检测脊髓组织L-脑啡肽（L-EK）浓度，所有大鼠均测基础痛阈值，并在第3天1、2、3、4、5周时测定大鼠右后爪机械痛阈值（PMWT）和热痛阈值（PWTL）。结果鞘内注射SHPZ后，外源人前脑啡肽原基因能有效表达，与对照组比较，SHPZ组PMWT和PTWL较注射前明显延长，于第1周开始差异有统计学意义（P〈0．05），于第3周达到高峰，镇痛作用可持续5周。结论鞘内注射人前脑啡肽原基因单纯疱疹病毒Ⅰ型扩增子载体对神经病理性疼痛大鼠有明显的镇痛作用。

英文摘要：

Objective To investigate the antinociceptive effect of intrathecal （IT） injection of Herpes simplex virus type Ⅰ（HSV-1） amplicon vector-mediated HPPE on chronic neuropathic pain. Methods 45 Sprague-Dawley rats underwent chronic constriction. Injury （CCI） of unilateral sciatic nerve and then were randomly divided into 3 equal groups： CCI ＋ normal saline group, undergoing insertion of mlcrospinal catheter into the subarachnoid space at the lumber region and intrathecal delivery of NS, CCI ＋ pHSVIRES -LacZ （SHPZ） group undergoing intrathecal delivery of and recombinant HSV-Ⅰ amplicon vector pHSVIRES-HPPE-LacZ containing human pre-proenkephalin （HPPE） gene, and CCI ＋ blank vector （SHZ） group receiving pHSV-HPPE-LacZ. Another 15 rats underwent sham operation to be used as control group. One week after IT administration 9 rats from each group were killed with their lumber segments of spinal cord removed to detect the expression of LacZ by X-gal staining, HPPE mRNA expression by RT-PCR, and L- enkephalin （L-EK） content by radioimmunoassay. Paw mechanical withdrawal threshold （PMWT） and paw withdrawal thermal latency （PWTL） were measured before CCI （baseline） and 3 days after CCI and then once a week for 5 weeks after IT administration. Results After IT administration of SHPZ expression of HPPE mRNA was detected in the spinal cord. One week after the IT injection the L-EK level of the SHPZ group was （748 ±185 ng/L） , significantly higher than those of the Sham operation, NS, and SHZ groups [ （452±89）, （453 ± 92）, and （451±99 ） ng/L respectively, all P 〈 0. 05 ]. The PWMT and PWTL levels of the SHPZ group were significantly increased since 1 week after the IT administration in comparison with the baseline values and those of the other 3 groups （ all P 〈 0. 05 ）, and these effects peaked in the third week and then lasted to the fifth week. However, the threshold to mechanical and thermal stimuli was not affected by intrathecal delivery of vehic