臂丛神经根性撕脱伤诱发小鼠前扣带回皮层内脑源性神经营养因子表达上调和焦虑情绪

Up-regulation of brain derived neurotrophic factor expression and anxiety in the anterior cingulate cortex of mice induced by brachial plexus root avulsion injury

目的探讨臂丛神经根性撕脱伤(brachial plexus avulsion,BPA)后小鼠前扣带回皮层(anterior cingulate cortex,ACC)内脑源性神经营养因子(brain derived neurotrophic factor,BDNF)的表达和小鼠焦虑情绪的发生情况。方法将成年雌性C57小鼠随机分为3组,包括假手术组(Sham组)、BPA组和撕脱伤+药物干预组(BPA+drug组),每组不少于6只,所有小鼠均行左侧臂丛神经造模。Sham组只显露臂丛神经,余不做任何处理;BPA组行前路颈7神经根撕脱造模;BPA+drug组于造模后鞘内给予BDNF特异性受体TrκB的拮抗剂ANA12。于术后7 d对小鼠ACC进行取材,行Western Blot及免疫荧光染色,分析BDNF及其相关蛋白的表达水平;于术后7和14 d对小鼠进行焦虑行为学检测,并进行统计学分析。结果 Western Blot及免疫荧光染色结果显示ACC内BDNF及其受体TrκB在撕脱伤后7 d表达明显升高,与Sham组相比,差异具有统计学意义(P<0.05);旷场实验及高架十字迷宫实验结果显示小鼠在撕脱伤后7 d即出现明显的焦虑情绪,可持续至术后14 d,与Sham组相比,差异具有统计学意义(P<0.05);同时,在给予药物TrκB拮抗剂处理后,上述小鼠焦虑行为被缓解,与BPA组相比,差异具有统计学意义(P<0.05)。结论 BPA可诱发小鼠ACC内BDNF表达升高,发生焦虑情绪;同时,ACC内BDNF可作为BPA诱发焦虑情绪的潜在治疗靶点。

Objective To investigate the expression of brain derived neurotrophic factor(BDNF)in anterior cingulate cortex(ACC)and the onset of anxiety emotion after brachial plexus avulsion(BPA)in mice.Methods Adult female C57 mice were randomly divided into 3 groups,including Sham operation group(Sham group),BPA group and avulsion injury+drug intervention group(BPA+drug group),with no less than 6 mice in each group.All the mice were made models of left brachial plexus.In Sham group,only the brachial plexus nerve was exposed without any treatment.In BPA group,the model of anterior cervical 7 nerve root avulsion was made.The BPA+drug group was given ANA12,the antagonist of BDNF specific receptor TrκB,through intrathecal injection after modeling.On the 7th day after operation,the ACC of mice was taken,and Western blot and immunofluorescence staining were performed to analyze the expression level of BDNF and its related proteins.At 7 and 14 days after operation,the anxiety behavior of mice was tested and statistically analyzed.Results Western blot and immunofluorescence staining showed that BDNF and its receptor TrκB in ACC increased significantly 7 days after avulsion injury,and the difference was statistically significant compared with Sham group(P<0.05).The results of open field test and elevated plus maze test showed that the mice showed obvious anxiety at 7 days after avulsion injury and lasted until 14 days after operation.The difference was statistically significant compared with Sham group(P<0.05).At the same time,after the treatment of the drug TrκB antagonist,the anxiety behavior of the above mice was relieved,and the difference was statistically significant compared with BPA group(P<0.05).Conclusion BPA can induce the up-regulation of BDNF in the ACC of mice and cause anxiety.At the same time,BDNF in ACC can be a potential therapeutic target for BPA-induced anxiety.