跑台运动上调BDNF/TrkB-CREB通路改善神经性疼痛模型大鼠焦虑样行为  

Treadmill exercise up-regulates BDNF/TrkB-CREB pathway to improve anxiety-like behavior in neuropathic pain rats

作　　者：王晓歌 鲍金宇 杨帅 吕怡杭 臧卫东[4] 李翠 WANG Xiaoge;BAO Jinyu;YANG Shuai;LYU Yihang;ZANG Weidong;LI Cui(School of Physical Education,Zhengzhou Technology and Business University,Zhengzhou 451400,China;College of Physical Education and Sports,Beijing Normal University,Beijing 100875,China;School of Physical Education(Main Campus),Zhengzhou University,Zhengzhou 450001,China;School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州工商学院体育学院,郑州451400 [2]北京师范大学体育与运动学院,北京100875 [3]郑州大学体育学院(校本部),郑州450001 [4]郑州大学基础医学院,郑州450001

出　　处：《中国实验动物学报》2024年第9期1149-1159,共11页Acta Laboratorium Animalis Scientia Sinica

基　　金：河南省自然科学基金(242300420378)。

摘　　要：目的本研究拟探究中低强度跑台运动对慢性坐骨神经压迫损伤(chronic constriction injury of the sciatic nerve,CCI)模型大鼠的痛行为和焦虑样行为的影响,并研究BDNF/TrkB-CREB通路参与运动缓解CCI大鼠疼痛及焦虑行为的神经机制。方法将32只SD雄性大鼠按照体重随机方法分为4组:假手术(Sham)组、模型(CCI)组、假手术+运动(Sham+Exe)组、模型+运动(CCI+Exe)组,其中Sham+Exe组、CCI+Exe组大鼠进行4周的跑台训练。在术前及术后不同时间点检测各组大鼠机械缩足阈值(paw withdrawal threshold,PWT)和热缩足潜伏期(paw withdrawal latency,PWL),采用高架十字迷宫实验和旷场实验评估大鼠的焦虑样行为,采用实时荧光定量逆转录PCR(real-time quantitative reverse transcription PCR,RT-qPCR)和免疫蛋白印迹实验检测海马组织中的脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、酪氨酸激酶受体(tyrosine kinase receptor B,TrkB)、环磷腺苷效应元件结合蛋白(cAMP-response element binding protein,CREB)的mRNA及蛋白表达。结果(1)CCI组大鼠术后7、14、21、28、35 d的术侧PWT和PWL显著低于Sham组(P<0.001),与CCI组相比,CCI+Exe组术侧PWT在21 d后显著增加(P<0.05),术侧PWL在14 d后显著增加(P<0.05);(2)与Sham组相比,CCI组大鼠停留在高架十字迷宫开放臂的时间百分比显著降低(P<0.001),在闭合臂的时间百分比显著升高(P<0.01),CCI+Exe组开放臂时间百分比较CCI组显著升高(P<0.05);(3)CCI组大鼠在旷场中央区域停留的时间百分比,较Sham组显著降低(P<0.001),CCI+Exe组与CCI组相比显著增加(P<0.05);(4)与Sham组相比,CCI组大鼠海马中的BDNF、TrkB、CREB mRNA和蛋白表达均显著降低(P<0.05,P<0.01),4周的跑台运动使BDNF、TrkB、CREB mRNA以及蛋白的表达显著增加(P<0.05)。结论四周跑台运动缓解了CCI模型大鼠的机械痛敏和热痛敏,并且缓解了慢性疼痛诱导的焦虑样行为;上调BDNF/TrkB-CREB通路可能是运动缓�Objective To investigate the effects of low-to-moderate intensity treadmill exercise on pain and anxiety-like behaviors in rats with chronic constriction injury of the sciatic nerve(CCI),and to explore the neural mechanism of the exercise-related brain-derived neurotrophic factor(BDNF)/tropomyosin receptor kinase B(TrkB)-cAMP-response element binding protein(CREB)pathway in relieving pain and anxiety behaviors in CCI rats.Methods Thirty-two D rats were divided randomly into four groups:sham group,CCI group,sham+exercise(Sham+Exe)group,and CCI+exercise(CCI+Exe)group.Rats in the exercise groups underwent treadmill training for 4 weeks.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were measured before and at different time points after the operation.The elevated plus maze(EPM)and open field test(OFT)were used to evaluate anxiety-like behaviors in the rats.mRNA and protein expression levels of BDNF,TrkB,and CREB in the hippocampus were detected by real-time quantitative reverse transcription PCR and Western Blot,respectively.Results(1)The PWT and PWL on the operative side of the rats were significantly lower in the CCI compared with the sham group at 7,14,21,28,and 35 days after the operation(P<0.001).The PWT on the ipsilateral side was significantly increased in the CCI+Exe group after 21 days compared with the CCI group(P<0.05),and the PWL on the ipsilateral side increased significantly after 14 days(P<0.05).(2)The EPM result showed that rats in the CCI group spent a significantly lower proportion of time in the open arms(P<0.001)and significantly more time in the closed arms compared with the sham group(P<0.01).Rats in the CCI+Exe group spent significantly more time in the open arms than the CCI group(P<0.05).(3)The OFT result showed that rats in the CCI group spent a significantly lower proportion of time in the central area of the open field compared with the sham group(P<0.001),while the percentage of time was significantly increased in the CCI+Exe group compared with the CCI group(P<0.05).(4)

关 键 词：跑台运动 神经病理性疼痛 焦虑 BDNF TRKB CREB 

分 类 号：Q95-33[生物学—动物学]