含NR1亚基的NMDA受体在骨癌痛大鼠痛觉过敏中的作用  

Role of NR1 subunit-containing NMDA receptors in hyperalgesia in rats with bone cancer pain

作　　者：朱倩梅 武林鑫 张博 董彦鹏 孙莉 Zhu Qianmei;Wu Linxin;Zhang Bo;Dong Yanpeng;Sun Li(Department of Anesthesiology,National Cancer Center National Clinical Research Center for Cancer Hospital Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021;Department of Anesthesiology,National Cancer Center National Clinical Research Center for Cancer Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518116,China)

机构地区：[1]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院,北京协和医学院肿瘤医院麻醉科,100021 [2]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院,北京协和医学院肿瘤医院深圳医院麻醉科,518116

出　　处：《中华麻醉学杂志》2020年第10期1242-1245,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81671099);深圳市二名工程项目:癌痛治疗及肿瘤围术期医学。

摘　　要：目的评价含NR1亚基的NMDA受体在骨癌痛大鼠痛觉过敏中的作用。方法清洁级健康雄性Wistar大鼠24只,6周龄,体重200~230 g,采用随机数字表法分为3组(n=8):假手术组(Sham组)、骨癌痛组(BCP组)和NR1 siRNA组(NR1组)。采用左侧胫骨骨髓腔注射乳腺癌Walker 256细胞混悬液制备大鼠骨癌痛模型。于造模开始后第10天,NR1组大鼠鞘内注射1 nmol/10μl NR1 siRNA 10μl,每48 h给药1次,连续4次。于造模前1 d(T_0)、造模后12~18 d(T_(1~7))时每天固定时间行热板实验和甩尾实验,于T_7时行为学测试结束后处死大鼠取L1~4脊髓组织,采用RT_-PCR法测定NR1 mRNA的表达。结果与Sham组相比,BCP组T_(1~7)时舔后足潜伏期缩短(P<0.05);与BCP组相比,NR1组T_(1~7)时舔后足潜伏期延长,T_2,7时甩尾潜伏期延长,T_7时脊髓NR1 mRNA表达下调(P<0.05)。结论含NR1亚基的NMDA受体参与了骨癌痛大鼠痛觉过敏的形成和维持。Objective To evaluate the role of NR1 subunit-containing N-methyl-D-aspartate receptor(NMDAR)in hyperalgesia induced by bone cancer pain(BCP)in rats.Methods T_wenty-four clean-grade male Wistar rats,aged 6 weeks,weighing 200-230 g,were divided into 3 groups(n=8 each)using a random number table method:sham operation group(Sham group),BCP group and NR1 siRNA group(NR1 group).BCP was induced by inoculating Walker 256 mammary gland carcinoma suspension into the medullary cavity of the left tibia.On the 10th day after establishing the model,1 nmol/10μl NR1 gene siRNA 10μl was intrathecally injected every 48 h for 4 consecutive times in NR1 group.Hot plate test and tail flick test were performed at 1 day before establishing the model(T_0),and 12-18 days after establishing the model(T_(1-7)).T_he animals were sacrificed after the end of behavioral test at T_7,and the lumbar segments of spinal cord(L1-4)were removed for determination of the expression of NR1 mRNA by real-time polymerase chain reaction.Results Compared with Sham group,the latency to hind-paw licking was significantly shortened at T_(1-7) in BCP group(P<0.05).Compared with BCP group,the latency to hind-paw licking was significantly prolonged at T_(1-7),the tail-flick latency was prolonged at T_2,7,and the expression of NR1 mRNA was down-regulated in NR1 group(P<0.05).Conclusion NR1 subunit-containing NMDAR is involved in the development and maintanence of hyperalgesia induced by BCP in rats.

关 键 词：骨肿瘤 疼痛 受体 N-甲基-D-天冬氨酸 痛觉过敏 

分 类 号：R738.1[医药卫生—肿瘤]