鞘内注射代谢性谷氨酸受体亚型3激动剂/拮抗剂对小鼠骨癌痛的影响  

Effects of intrathecal of metobotropic glutamate receptor 3 agonist/antagonist on mice with bone cancer pain

作　　者：孙大鹏[1] 任炳旭[1] 季永[1] 唐季春[1] 李国君[1] 杨定清[1] 朱小莲[1] 孙海燕[1] 

机构地区：[1]江南大学附属医院麻醉科,江苏无锡214062

出　　处：《中国现代医学杂志》2014年第20期1-5,共5页China Journal of Modern Medicine

基　　金：国家自然科学青年基金(No:81300949);江苏省自然科学青年基金(No:BK2012102);无锡市医院管理中心医学科技发展基金(No:YGM1108)

摘　　要：目的探讨代谢性谷氨酸受体亚型3(mGluR3)对骨癌痛的影响及机制。方法 C3H/HeNCrlVr雄性小鼠84只随机分为:1正常组;2APDC+Tumor组;3DMSO+Tumor组;4APDC+Sham组;5DMSO+Sham组;6LY341495+Tumor组;7LY341495+Sham组。用热辐射刺激仪测定缩足潜伏期(PWTL)。应用Real-time PCR和Western blotting技术检测mRNA和蛋白的表达。结果术后14 d,与正常组相比,假手术组PWTL差异无统计学意义,而骨癌痛组PWTL明显降低(P<0.05)。术后21 d,和正常组相比,APDC+Sham组、DMSO+Sham组PWTL和脊髓GFAP、IL-1β、IL-6、TNF-α表达差异均无统计学意义;DMSO+Tumor组PWTL(6.18±1.29)s明显低于正常组(15.91±1.65)s,脊髓GFAP、IL-1β、IL-6、TNF-α表达则高于正常组(P<0.05);APDC+Tumor组PWTL(9.39±1.94)s高于DMSO+Tumor组,脊髓GFAP、IL-1β、IL-6、TNF-α表达则低于DMSO+Tumor组(P<0.05);LY341495+Tumor组PWTL(6.09±0.26)s、脊髓GFAP、IL-1β、IL-6、TNF-α表达水平与DMSO+Tumor组差异无统计学意义;LY341495+Sham组PWTL(11.89±2.95)s低于DMSO+Sham组(16.57±1.86)s,脊髓GFAP、IL-1β、IL-6、TNF-α表达则高于DMSO+Sham组(P<0.05);和术后14 d(注药前)相比,APDC+Tumor组PWTL值升高(P<0.05),DMSO+Tumor组、LY341495+Tumor组和LY341495+Sham组PWTL值则降低(P<0.05)。结论鞘内注射mGluR3激动剂APDC具有抗癌痛作用,而鞘内注射mGluR3拮抗剂LY341495促进伤害性感受,调控星形胶质细胞活化,释放炎症因子可能是其机制之一。[Objective] To investigate the role of spinal metabotropic glutamate receptor 3 （mGluR3） in bone cancer pain and its mechanism. [Methods] C3H/HeNCrlVr 84 male mice were randomly divided into： normal control group： The mice were given food and water ad libitum; APDC ＋ Tumor group： Tumor mice were treated by intrathecal administration （once daily on the days 14 -20 after inoculation of tumor cells） with the mGluR3 agonist APDC 150 nmol; DMSO ＋ Tumor group： Tumor mice were treated with the same volume of DMSO; APDC ＋ Sham group： Sham mice were treated with the same dose of APDC; DMSO ＋ Sham group： Sham mice were treated with the same volume of DMSO; LY341495 ＋ Tumor group： Tumor mice were treated with the mGluR3 antagonist LY341495 15 nmol; LY341495 ＋ Sham group： Sham mice were treated with the same dose of LY341495. Pain behaviors were assessed with the paw withdrawal thermal latency （PWTL） at the corresponding time points, then the mice were killed and the samples of spinal cord were used to Real-time PCR and western blotting. [Results] At day 14 after operation, compared with the normal group, no significant difference was found in the PWTL value between normal control group and sham operation group. But the PWTL value of tumor group, was significantly lower than that of normal control group （P 〈0.05）. At day 21 after operation, the PWTL and the level of spinal GFAP, IL-1β, IL-6, TNF-α expression had no significant differences among normal control group, APDC ＋ Sham group and DMSO ＋ Sham group; and the PWTL （6.18 ± 1.29 s） of DMSO ＋ Tumor group was significantly lower than that of normal control group （15.91± 1.65 s） （P〈0.05）, but the level of GFAP, IL-113, IL-6, TNF-o- expression was higher than that of normal control group; compared with the normal group, the PWTL （9.39 ±1.94 s） of APDC ＋ Tumor group was higher, and the level of spinal GFAP, IL-1β, IL-6, TNF-α expression was lower （P〈0.05）; the PWTL and the level of spinal GFAP

关 键 词：骨癌痛 代谢性谷氨酸受体亚型3 星形胶质细胞 胶质细胞纤维酸性蛋白 炎症因子 

分 类 号：R441.1[医药卫生—诊断学] R364.5[医药卫生—临床医学]