水溶性脂质体运载siRNA对神经病理性疼痛大鼠脊髓NMDA受体1的影响

Water soluble lipopolymer can be an efficient carrier of NMDAR1siRNA to rats with neuropathic pain

目的探讨水溶性脂质体(WSLP)运载N-甲基-D-天冬氨酸受体1(N-methyl-D-aspartate receptor1,NMDAR1)利用小干扰RNA(small interference RNA,siRNA)治疗神经病理性疼痛的可行性。方法采用坐骨神经分支选择结扎切断(spared nerve injury model,SNI)制作神经病理性疼痛大鼠模型,选取鞘内置管成功SD大鼠24只,随机均分为四组:S组,仅暴露坐骨神经,不结扎;C组,SNI+鞘内注射生理盐水;W组,SNI+鞘内注射WSLP/siRNA混合物;L组,SNI+鞘内注射乱序siRNA与WSLP混合物。通过实时定量PCR和western-blot技术分别检测各组大鼠脊髓背角NMDAR1 mRNA相对表达和NMDAR1蛋白表达水平的变化。结果 C组和L组第4天脊髓背角NMDAR1 mRNA相对表达和NMDAR1蛋白表达水平显著高于S、W组(P<0.05)。结论 WS-LP可有效运载siRNA抑制神经病理性疼痛大鼠NMDAR1的过度表达。

Objective To examine the effectiveness of water soluble lipopolymer （WSLP） for delivering N-methyl-D-aspartate receptor 1 （NMDAR1） small interference RNA（siRNA） in rats with neuropathic pain. Methods TWenty four SD rats undergoing spared nerve injury （SNI） were randomly allocated into four groups with six each： control group （group C） received intrathecal saline, siRNA group （group W） received NMDAR1 siRNA complexed with WSLP, siRNA group （group L） received scrambled siRNA complexed with WSLP, and sham group （group S） merely expose sciatic nerve. Changes of NMDAR1 expression were detected using real-time PCR and western blotting in spinal cord. Results The expression levels of both NMDAR1 mRNA and protein in the spinal cord in groups C and L were higher than that of groups W and S（P〈0. 05）. Conclusion WSLP can deliver NMDA R1 siRNA in vivo, and suggests that intrathecal injection of WSLP/NMDAR1/ siRNA may be a method for neuropathic pain treatment.