| 于婷,成洪聚,辛青,许飞,李雷.外源性脑源神经营养因子降低糖尿病大鼠痛阈的机制研究[J].济宁医学院学报,2019,42(4):238-243 |
| 外源性脑源神经营养因子降低糖尿病大鼠痛阈的机制研究 |
| Study on the mechanism of exogenous brain-derived neurotrophic factor in relieving pain symptoms of diabetic rats |
| 投稿时间：2017-03-08 |
| DOI：10.3969/j.issn.1000-9760.2019.04.003 |
| 中文关键词: 脑源性神经营养因子;酪氨酸激酶受体B;背根神经节;神经元;糖尿病神经病变 |
| 英文关键词: Brain-derived neurotrophic factor;Tropomyosin-receptor-kinase B;Neuron;Dorsal root ganglion;Diabetic neuropathy |
| 基金项目:济宁市科技助推新旧动能转换计划（2017SMNS004）；济宁市科技发展计划（2014jnyx05） |
| 作者 | 单位 | E-mail | | 于婷 | 济宁医学院基础医学院, 济宁 272067 | | | 成洪聚 | 济宁医学院基础医学院, 济宁 272067 | | | 辛青 | 济宁医学院基础医学院, 济宁 272067 | | | 许飞 | 济宁医学院附属济宁市第一人民医院, 济宁 272011 | | | 李雷 | 济宁医学院临床医学院, 济宁 272013 | iampolkers@163.com |
|
| 摘要点击次数: 2620 |
| 全文下载次数: 926 |
| 中文摘要: |
| 目的 探讨外源性脑源神经营养因子（BDNF）及其高亲和力受体酪氨酸激酶受体B（TrkB）对糖尿病周围神经病变（DPN）大鼠的痛觉过敏症状的作用及其机制。方法 利用链脲佐菌素（STZ）建立DPN模型大鼠，将DPN模型大鼠随机分为BDNF组、TrkB Fc组和DPN组，每组16只，鞘内置管给予不同药物，BDNF组给予BDNF，TrkB组给予BDNF+TrkB Fc（由TrkB受体的细胞外配体结合结构域组成的合成融合蛋白），DPN组给予DMSO溶剂。用von Frey纤维检测机械痛觉阈值，用热痛仪检测热痛觉阈值。用荧光实时定量PCR检测大鼠背根神经节（DRG）组织BDNF和TrkB的mRNA表达，蛋白印迹检测BDNF和TrkB蛋白表达。用全细胞膜片钳电流钳检测DRG神经元静息电位水平、阈电流强度及动作电位频率。结果 与DPN组相比较，BDNF组鞘内注射BDNF升高机械痛觉和热痛觉阈值，并且降低DRG神经元的过度兴奋，这些效应可被预先给予TrkB Fc所阻断，差异具有统计学意义（均P<0.05）。与DPN组相比较，鞘内给予BDNF对DRG中BDNF和TrkB表达无显著影响，差异不具有统计学意义（均P>0.05）。结论 外源性BDNF通过降低DRG神经元的过度兴奋缓解DPN大鼠的疼痛症状，BDNF可能是潜在的治疗糖尿病性神经病理性疼痛的新型药物。 |
| 英文摘要: |
| Objective To investigate the role of exogenous brain-derived neurotrophic factor (BDNF) and its high-affinity tropomyosin-receptor-kinase B (TrkB) in rats with peripheral neuropathy (DPN). Methods The intraperitoneal injection of streptozotocin (STZ) was used to establish the DPN rat model.The DPN rats were randomly divided into BDNF group,TrkB group and DPN group.There are 16 rats in each group.The intrathecal tube was used to give different drugs.BDNF group was given BDNF.TrkB group was given BDNF + TrkB Fc (a synthetic fusion protein consisting of the extracellular ligand-binding domain of the TrkB receptor).And DPN group was given DMSO solvent.The mechanical pain threshold was measured with von Frey filaments and the thermal threshold was measured with a plantar analgesia tester.The expression of BDNF and TrkB mRNA in dorsal root ganglion (DRG) tissues was detected by real-time PCR.The expression of BDNF and TrkB protein was detected by Western blotting.The whole-cell current clamp recording was performed to determine resting potential,rheobase and action potential frequency of DRG neurons. Results Compared with DPN group,intrathecal administration of BDNF dramatically elevated mechanical and thermal thresholds as well as inhibited hyperexcitability of DRG neurons.These effects were blocked by pretreatment with TrkB Fc.Compared with DPN group,intrathecal administration of BDNF did not affect the expression of BDNF and TrkB in DRG. Conclusion Exogenous BDNF relieved pain symptoms of DPN rats by reducing hyperexcitibility of dorsal root ganglion neurons which might be the potential treatment of painful diabetic neuropathy. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
