脊髓p300在大鼠CCI所致神经病理性疼痛中的作用

目的 探索脊髓p300在大鼠慢性缩窄性神经损伤（CCI）模型所致神经病理性疼痛中的作用.方法 32只雄性SD大鼠随机分为假手术组（Sham组）和CCI组,24只大鼠鞘内置管后制作CCI模型,随机分为3组：二甲基亚砜（DMSO）组、p300乙酰转移酶抑制剂C646组和对照剂C37组.术后第7天开始鞘内给药直至第14天,观察大鼠机械痛阈变化,术后第14天利用免疫荧光及Western blot检测脊髓p300的表达分布.结果 （1）p300主要表达于神经元中,且CCI组表达量高于Sham组（P＜0.05）.（2）鞘内注射C646明显提高CCI大鼠机械痛阈,而注射C37和DMSO后大鼠痛阈无明显变化.结论 大鼠脊髓p300蛋白参与神经病理性疼痛,其机制可能与其乙酰转移酶活性有关.

The role of spinal cord p300 in chronic constriction nerve injury-induced neuropathic pain in rats

Objective To explore the role of spinal cord p300 in neuropathic pain induced by chronic constriction nerve injury （CCI） in rats.Methods Thirty two Sprague-Dawley （SD） rats were randomly divided into sham and CCI groups,14 days after surgery,immuno-fluorescence staining and Western blot were used to detect distribution and expression of p300 protein.After rats were successfully implanted with an intrathecal catheter and accepted CCI surgery,another 24 rats were randomly divided into three groups （n =8）：dimethyl sulfoxide （DMSO） group,p300 acetyltransferase inhibitor C646 group,and control C37 group.Each rat were administered through the intrathecal catheter from day 7 to 14 and mechanical withdraw threshold were tested.Results （1） The p300 positive cells were detected mainly in neurons,and p300 protein in spinal cord of CCI group were significantly higher than sham group （P ＜0.05）.（2） C646 alleviated significantly neuropathic pain in rats,without significant changes in pain threshold after injection of C37 and DMSO.Conclusions The p300 protein in spinal cord was involved in the development of neuropathic pain in rats,the mechanism may be referred to its acetyltransferase activity.