中文摘要：

目的 探讨鞘内注射PSD-93反义寡核苷酸对大鼠神经病理性痛的疗效。方法 雄性SD大鼠60只，随机分为5组（n=12）：假手术组（S组）、C，脊神经压迫组（N组）、C7脊神经压迫＋鞘内注射PSD-93误义寡核苷酸10μg组（M组）、C7脊神经压迫＋鞘内注射PSD-93反义寡核苷酸5μg组（A1组）和C7脊神经压迫＋鞘内注射PSD-93反义寡核苷酸10μg组（A2组）。N组、M组、A1组和赴组用60g无创微血管夹压迫大鼠右侧C7脊神经15min，制备神经病理性痛模型，经枕骨大孔鞘内置管，术毕当日开始给药，每日1次，连续4d。于术前2d（T0）和术后1、3、5、7d（T1-4）测定机械痛阈和热痛阈；T2和T4时分别处死6只大鼠，取C7脊髓，免疫组化法测定脊髓背角PSD-93蛋白表达。结果 与S组比较，N组、M组和A1组T1-4时机械痛阈及热痛阂降低，N组和M组T2-4时脊髓背角PSD-93蛋白表达上调（P〈0．05）；与N组和M组比较，A1组T1,2时、A2组T1-4时机械痛阈及热痛阈升高，A1组T2时、A2组T2,2．4时脊髓背角PSD-93蛋白表达下调（P〈0.05）；与A1组比较，A2组T2.4时机械痛阈及热痛阈升高，T2.4时脊髓背角PSD-93蛋白表达下调（P〈0．05）。结论 鞘内注射PSD-93反义寡核苷酸可减轻大鼠神经病理性痛。

英文摘要：

Objective To investigate the effects of intratheeal （IT） PSD-93 antisense oligonueleotide （ASODN） on the expression of PSD-93 protein in the dorsal horn of the spinal cord in a rat model of neuropathie pain. Methods Sixty male SD rats weighing 250-350 g were used in this study. The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg. Neuropathie pain was produced by clamping the fight C7 spinal nerve for 15 rain with a 60 g atraumatie mini-clamp （C7 SNC）. A catheter was placed in subaraehnoid space via foramen magnum according to Yaksh. The tip of the catheter reached C7 The animals were randomly divided into 5 groups （n = 12 each） ： group Ⅰ sham operation （S）; group ⅡC7 SNC ＋ normal saline （NS） （N）; group Ⅲ C7 SNC ＋ mismatch oligonueleotide （MSODN） （M） ; group Ⅳ C7 SNC ＋ ADODN 5 μg （AS1） and groupV C7 SNC ＋ ADODN 10 μg （ AS2 ）. Normal saline or MSODN or ADODN was administered IT once a day for 4 consecutive days after operation. Paw withdrawal threshold （PWT） to noxious thermal and mechanical stimuli were measured before surgery （To ,baseline） and on the 1st, 3rd, 5th and 7th day after operation （T1-4 ）. Six animals were killed at T2 and T4 respectively in each group and the C7 segment of the spinal cord was removed for determination of the PSD-93 protein expression in the dorsal horn of spinal cord by immuno-histoehemistry. Results Thermal and mechanical hyperalgesia was induced by C7 SNC and was significantly inhibited by IT ADODN dose-dependently. The expression of PSD-93 protein in spinal dorsal horn was significantly up-regulated by C7 SNC. The up-regulated PSD-93 protein expression was significantly decreased by IT ADODN dose-dependently. Conclusion Intrathecal PSD-93 ASODN can reduce neuropathic pain induced by C7 SNC by reducing spinal PSD-93 protein expression.