GLP-1受体在神经病理性疼痛大鼠焦虑样行为中的作用  

ROLES OF GLP-1 RECEPTOR IN NEUROPATHIC PAIN-INDUCED ANXIETY-LIKE BEHAVIOR

作　　者：崔珊珊 詹丽英[1] 冯晓波[2] 丁煌 柯剑娟[2] CUI Shan-Shan;ZHAN Li-Ying;FENG Xiao-Bo;DING Huang;KE Jian-Juan(Department of Anesthesiology,Renmin Hospital Wuhan University,Hubei province,430060,China;Department of Anesthesiology,Zhongnan Hospital Wuhan University,Hubei province,430071,China)

机构地区：[1]武汉大学人民医院麻醉科,武汉430060 [2]武汉大学中南医院麻醉科,武汉430071

出　　处：《中国疼痛医学杂志》2019年第6期409-413,419,共6页Chinese Journal of Pain Medicine

基　　金：中央引导地方科技发展专项资金(2060403)

摘　　要：目的:观察大鼠前额叶皮质、海马、杏仁核内胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)受体在神经病理性疼痛大鼠焦虑样行为中的作用。方法:50只体重200~250 g的SD大鼠随机分为正常组(Normal)、对照组(Sham)、SNL组、SNL+saline组、SNL+exendin-4组,每组10只,其中SNL+exendin-4组于术后第14~20 d鞘内给与GLP-1R激动剂exendin-4。采用左侧L5脊神经结扎(spinal nerve ligation model,SNL)制备大鼠慢性神经病理性疼痛模型。采用von Frey监测大鼠机械性触诱发痛,采用高架十字迷宫测试和强迫游泳评价大鼠的焦虑样行为,Western blot观察五组大鼠前额叶皮质、海马、杏仁核内GLP-1R蛋白表达。结果:左侧L5脊神经结扎大鼠在术后第3d表现明显的机械痛阈降低,并持续至术后21 d,鞘内给予GLP-1R激动剂exendin-4后大鼠痛阈显著增加。SNL大鼠在高架十字迷宫中的开放臂进入次数百分比和开放臂停留时间百分比显著缩短,大鼠挣扎游泳时间较对照组显著降低,即出现了焦虑样行为,鞘内注射GLP-1R受体激动剂exendin-4,其挣扎游泳时间延长,在高架十字迷宫实验开放臂进入次数百分比和开放臂停留时间百分比均显著增加,即焦虑样行为改善;与对照组比较,SNL大鼠前额叶皮质、海马、杏仁核内的胰高血糖素样肽-1结合受体(glucagon-like peptide-1 receptor,GLP-1R)蛋白含量均显著下降,鞘内注射exendin-4后大鼠各脑区GLP-1R含量显著增高(P<0.05)。结论:长期慢性疼痛可诱导大鼠焦虑样行为,其机制可能是通过降低前额叶皮质、海马、杏仁核内的GLP-1R表达。Objective:To explore roles of glucagon-like peptide-1(GLP-1)receptor in the prefrontal cortex,hippocampus and amygdaloid nucleus of rats in neuropathic pain-induced anxiety-like behavior.Methods:Fifty male SD rats,weighing 200-250 g,were randomly divided into 5 groups(n=50)using a random number table:Normal group,Sham group,SNL group,SNL+saline group and SNL+exendin-4 group,10 rats in each group.In sham group,L5 spinal nerve was not ligated.In SNL group,left L5 spinal nerve ligation model(SNL)was established.Group SNL+saline or group SNL+exendin-4 was intrathecally infused with NS or exendin-4 from day 14 to day 21 after SNL operation.The mechanical threshold of tactile allodynia was examined with von Frey filaments.The test of depression-like behavior was performed by forced swimming test and the elevated plus maze.Glucagon-like peptide-1 receptor(GLP-1R)expression in prefrontal cortex,hippocampus and amygdaloid nucleus were determined by western bolt.Results:SNL induced a significant reduction of the mechanical threshold of tactile allodynia from day 1 to day 21(P<0.05)and the most prominent time point of hyperalgesia is day 3.However intrathecal injection of exendin-4 could increase pain threshold(P<0.05).The elevated plus maze experiments and the forced swimming tests showed that the rats in SNL group were significantly hypoactive and more anxious than normal group(P<0.05),however intrathecal injection of GLP-1R agonist exendin-4 significantly facilitated anxiety extinction(P<0.05).In addition,the expression levels of GLP-1R in prefrontal cortex,hippocampus and amygdaloid nucleus was significantly reduced in SNL group and SNL+saline group(P<0.05),and exendin-4 prevented SNL-induced down-regulation of GLP-1R(P<0.05).Conclusion:The long-lasting chronic pain could induce anxiety-like behavior,and its mechanism may be related to the decreased GLP-1R level in prefrontal cortex,hippocampus and amygdaloid nucleus.

关 键 词：慢性疼痛 胰高血糖素样肽-1结合受体 焦虑样行为 前额叶皮质 海马 杏仁核 

分 类 号：R741[医药卫生—神经病学与精神病学]