鞘内注射PSD-93反义寡核苷酸对大鼠神经病理性痛的疗效

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)、C7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10 μg组(M组)、C7脊神经压迫+鞘内注射PSD-93反义寡核苷酸5 μg组(AJ组)和C7脊神经压迫+鞘内注射PSD-93反义寡核苷酸10 μg组(A2 组).N组、M组、A1组和A2组用60 g无创微血管夹压迫大鼠右侧C7脊神经15 min,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4 d.于术前2 d(T0)和术后1、3、5、7 d(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时机械痛阈及热痛阈降低,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T2,4时脊髓背角PSD-93蛋白表达下调(P＜0.05);与A1组比较,A2组T1-4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.

Effects of intrathecal PSD-93 antisense oligonucleotide OR the PSD-93 protein expression in spinal cord in a rat model of neuropathic pain

Objective To investigate the effects of intrathecal(IT)PSD-93 antisense oligonucleotide(ASODN)on the expression of PSD-93 protein in the dorsal horn of the spinal cord in a rat model of neuropathic pain.Methods Sixty male SD rals weighing 250-350 g were used in this study.The animals were anesthetized with intraperitoneal 10% choral hydrate 350 mg/kg.Neuropathic pain was produced by clamping the right C7 spinal nerve for 15 min with a 60 g atraumatic mini-clamp(C7 SNC).A catheter was placed in subarachnoid space via foramen rnagnum 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 Ⅱ C7 SNC+normal saline(NS)(N);group Ⅲ C7 SNC+mismatch oligonucleotide(MSODN)(M);group Ⅳ C7 SNC+ADODN 5μg(AS1)and group Ⅴ C7 SNC+ADODN 10μg(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(T0,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-histochemistry.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 significandy decreased by IT ADODN dose-dependendy.Conclusion Intrathecal PSD-93 ASODN can reduce neuropathie pain induced by C7 SNC by reducing spinal PSD-93 protein expression.