脊髓组蛋白甲基化在大鼠神经病理性痛维持中的作用  

Role of histone methylation in spinal cord in maintenance of neuropathic pain in rats

作　　者：牛敏[1] 张博[1] 张军[1] 耿立成[1] 

机构地区：[1]天津市人民医院麻醉科,300191

出　　处：《中华麻醉学杂志》2015年第11期1318-1320,共3页Chinese Journal of Anesthesiology

摘　　要：目的 评价脊髓组蛋白甲基化在大鼠神经病理性痛维持中的作用.方法 健康雄性Wistar大鼠60只,体重200～ 250 g,6～8周龄,采用随机数字表法分为5组（n=12）：对照组（C组）、假手术组（S组）、神经病理性痛组（NP组）、毛壳素组（CH组）和二甲基亚砜组（DMSO组）.NP组、CH组和DMSO组采用慢性压迫性损伤（CCI）法制备神经病理性痛模型,S组仅暴露出坐骨神经,不予结扎.CCI后第2天,CH组鞘内注射H3K9甲基转移酶抑制剂毛壳素50μg,DMSO组鞘内注射等容量二甲基亚砜,连续4d.分别于CCI前1 d（T0）和CCI后第2天给药前（T1）、CCI后5 d（T2）、7d（T3）、9 d（T4）、14 d（T5）时,测定大鼠机械缩足反应阈（MWT）和热缩足潜伏期（TWL）.分别于T3和T5痛阈测定结束后,处死6只大鼠,取脊髓组织,采用免疫组化法检测甲基化H3K9表达水平.结果 与C组比较,S组各时点MWT、TWL和脊髓甲基化H3K9表达差异无统计学意义（P＞0.05）,NP和DMSO组T1-5时MWT降低,TWL缩短,T3和T5时脊髓甲基化H3K9表达上调,CH组T1时MWT降低,TWL缩短（P＜0.05）;与NP组比较,CH组T2-5时MWT升高,TWL延长,T3和T5时脊髓甲基化H3K9表达下调（P＜0.05）,DMSO组各时点MWT、TWL和脊髓甲基化H3K9表达差异无统计学意义（P＞0.05）.结论 脊髓组蛋白甲基化参与了大鼠神经病理性痛的维持.Objective To evaluate the role of histone methylation in the spinal cord in maintenance of neuropathic pain （NP） in rats.Methods Sixty healthy male Wistar rats, weighing 200-250 g, aged 6-8 weeks, were randomly divided into 5 groups （n =12 each） using a random number table： control group （C group）, sham operation group （S group）, NP group, chaetocin group （CH group）, and dimethyl sulfoxide （DMSO） group.NP was induced by chronic constriction injury （CCI） to the sciatic nerve in NP, CH and DMSO groups.The sciatic nerve was only exposed in group S.H3K9 methylation methyltransferase inhibitor chaetocin 50 μg was injected intrathecally in group CH, and the equal volume of DMSO was given instead in group DMSO for 4 consecutive days, starting from 2nd day after CCI.The mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured before CCI （T0）,before administration on 2nd day after CCI （T1）, and at 5, 7, 9 and 14 days after CCI （T2-5）.Six rats in each group were sacrificed after measurement of pain threshold at T3 and T5, and the lumbar segment of the spinal cord was removed for detection of the methylated H3K9 expression by immunohistochemistry.Results Compared with C group, no significant change was found in the MWT, TWL and methylated H3K9 expressionat each time point in S group （P〉0.05） , the MWT was significantly decreased, and the TWL was shortened at T1-5, and the methylated H3K9 expression was up-regulated at T3 and T5 in NP and DMSO groups, and the MWT was significantly decreased, and the TWL was shortened at T1 in CH group （P〈 0.05）.Compared with NP group, the MWT was significantly increased, and the TWL was prolonged at T2-5, and the methylated H3K9 expression was down-regulated at T3 and T5 in CH group （P〈0.05） , and no significant change was found in the MWT, TWL and methylated H3K9 expression at each time point in DMSO group （P〉0.05）.Conclusion Histone methylation in the spinal cord is involved i

关 键 词：甲基化 组蛋白类 脊髓 神经痛 

分 类 号：R614[医药卫生—麻醉学]