摘要
背景:神经病理性疼痛的发生及其所致抑郁可能与大脑皮质代谢型谷氨酸受体5和N-甲基-D-天冬氨酸受体2B型蛋白表达增加有关。目的:探索坐骨神经慢性压迫性损伤大鼠疼痛及其所致抑郁的行为学特点,并观察神经病理性疼痛大鼠左侧无粒型岛皮质背侧区代谢型谷氨酸受体5和N-甲基-D-天冬氨酸受体2B型蛋白表达情况。方法:采用随机数字表法将50只SD大鼠分为假手术组(仅暴露坐骨神经干,不予结扎)和模型组(结扎坐骨神经建立坐骨神经慢性压迫性损伤模型)。于术后1-5周每周使用Von Frey纤维丝检测大鼠机械痛敏缩足阈值;通过糖水偏爱法和强迫游泳法观察抑郁样行为;术后5周采用坐骨神经功能指数及苏木精-伊红染色观察坐骨神经功能及结构状态,通过[18]F-FDG PET-CT观察坐骨神经及大脑代谢情况,采用免疫印迹检测大脑左侧无粒型岛叶皮质背侧区中代谢型谷氨酸受体5和N-甲基-D-天冬氨酸受体2B型表达水平。结果与结论:(1)与假手术组大鼠相比,模型组大鼠机械痛敏缩足阈值和坐骨神经功能指数在术后1周开始显著降低(P<0.05),于2,3周出现明显抑郁样行为并进行性加重(P<0.05);(2)苏木精-伊红染色提示模型组坐骨神经病理改变呈进行性加重;模型组大鼠右侧坐骨神经/肝脏平均标准化摄取值自术后2-4周较假手术组显著增加(P<0.05);(3)术后5周,模型组大鼠大脑左侧无粒型岛叶皮质背侧区中代谢型谷氨酸受体5和N-甲基-D-天冬氨酸受体2B型表达水平较假手术组明显增高(P<0.05);(4)结果说明,坐骨神经损伤后所致机械疼痛、抑郁样行为、坐骨神经功能和病理表现并不完全同步。左侧无粒型岛皮质背侧区中代谢型谷氨酸受体5和N-甲基-D-天冬氨酸受体2B型可能参与神经病理性疼痛和疼痛所致抑郁样行为的发病机制。
BACKGROUND:The occurrence of neuropathic pain and the resulting depression may be related to the increased protein expression of metabotropic glutamate receptor 5(mGluR5)and N-methyl-D-aspartate receptor type 2B(NMDAR2B)in the brain.OBJECTIVE:To explore the behavioral characteristics of pain and depression in rats with neuropathic pain caused by chronic compressive injury of the sciatic nerve and to observe the expression of mGluR5 and NMDAR2B proteins in the left dorsal agranular insular area of the rats with neuropathic pain.METHODS:Fifty Sprague-Dawley rats were divided into sham operation group(n=25;only the sciatic nerve trunk was exposed without ligation)and model group(n=25;the sciatic nerve was ligated to establish a chronic compressive injury model).Von Frey filaments were used to detect mechanical paw withdrawal threshold in rats.Depression-like behaviors were observed by the sugar water preference test and forced swimming test.The sciatic nerve function index and hematoxylin-eosin staining were used to observe the function and structure of the sciatic nerve.The metabolism of the sciatic nerve and brain was observed by[18]F-FDG PET-CT.The expression levels of mGluR5 and NMDAR2B in the left-brain dorsal agranular insular area were detected by western blot.RESULTS AND CONCLUSION:Compared with the sham operation group,the mechanical paw withdrawal threshold and sciatic nerve function index were significantly decreased in the model group at 1 week after operation(P<0.05),and depression-like behaviors appeared and progressively worsened in 2-3 weeks(P<0.05).Hematoxylin-eosin staining results showed that the pathological changes of the sciatic nerve in the model group were progressively aggravated.The average standardized intake value of the right sciatic nerve/liver in the model group was significantly higher than that in the sham operation group in 2-4 weeks after operation(P<0.05).The expression levels of mGluR5 and NMDAR2B in the left dorsal agranular insular area were significantly higher in the model gr
作者
胡月
朱垸樑
万腾刚
胥方元
胥章彧
李佶钖
李丹
王剑雄
Hu Yue;Zhu Yuanliang;Wan Tenggang;Xu Fangyuan;Xu Zhangyu;Li Jiyang;Li Dan;Wang Jianxiong(Department of Rehabilitation Medicine,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第20期3216-3223,共8页
Chinese Journal of Tissue Engineering Research
基金
西南医科大学校级科研项目(2021ZKQN042),项目负责人:胡月
西南医科大学校级科研项目(2019ZQN110),项目负责人:王剑雄
四川省医学会青年创新科研项目(Q19035),项目负责人:王剑雄。
