摘要
目的:探究大麻二酚(CBD)通过脑源性神经营养因子(BDNF)/酪氨酸激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路对大鼠抑郁行为的影响。方法:60只SPF级雄性SD大鼠随机分为正常对照组,模型组,低、高剂量CBD组(CBD-L、CBD-H组)和高剂量CBD+BDNF抑制剂K252a组(CBD-H+K252a组),每组12只。除正常对照组外,余48只大鼠采用尾静脉注射皮质酮构建大鼠抑郁模型。CBD-L组、CBD-H组大鼠腹腔分别注射5、10 mg/kg的CBD溶液,CBD-H+K252a组大鼠腹腔注射10 mg/kg CBD溶液+100μg/kg K252a溶液,模型组和正常对照组腹腔注射等体积生理盐水。各组均每日给药1次,连续3周。采用糖水偏好实验、强迫游泳实验和旷场实验评估大鼠的抑郁行为;TUNEL染色法观察大鼠海马组织神经元凋亡情况;ELISA法检测各组大鼠海马组织中IL-6、IL-1β、NE、5-HT、DA水平。Western blot法测定海马组织中BDNF、TrkB蛋白表达及CREB磷酸化水平。结果:与正常对照组比较,模型组大鼠糖水偏好率、自主活动评分、海马组织NE、5-HT、DA水平、BDNF、TrkB蛋白表达和CREB磷酸化水平降低,在水中不动时间、海马组织IL-6、IL-1β水平、细胞凋亡率升高(P<0.05),海马组织神经元排列疏松紊乱,出现核固缩,且尼氏小体大量丢失。与模型组比较,CBD-L组、CBD-H组大鼠上述指标变化相反(P<0.05)。K252a可减弱CBD-H对模型大鼠抑郁样行为的改善作用(P<0.05)。结论:CBD能够改善皮质酮致大鼠抑郁行为,其机制可能与激活BDNF/TrkB/CREB信号通路有关。
Aim:To explore the effect of cannabidiol(CBD)on depressive behavior in rats through the brain-derived neurotrophic factor(BDNF)/tyrosine kinase receptor B(TRkB)/cyclic adenosine monophosphate response element-binding protein(CREB)signaling pathway.Methods:A total of 60 SPF grade male SD rats were randomly divided into the normal control group,the model group,the low-dose and high-dose CBD groups(CBD-L and CBD-H groups),and the high-dose CBD+BDNF inhibitor K252a group(CBD-H+K252a group),with 12 rats in each group.Except for the rats in normal control group,the remaining 48 rats were injected with corticosterone via the tail vein to establish a rat depression model.Rats in the CBD-L group and the CBD-H group were intraperitoneally injected with 5,10 mg/kg CBD solution respectively.Rats in the CBD-H+K252a group were intraperitoneally injected with 10 mg/kg CBD solution and 100μg/kg K252a solution.The model group and the normal control group were intraperitoneally injected with the same volume of normal saline.Each group was administered once a day for 3 consecutive weeks.The depressive behaviors of rats were evaluated by sugar water preference test,forced swimming test and open field test.The apoptosis of neurons in the hippocampal tissue of rats was observed by TUNEL staining.The levels of IL-6,IL-1β,NE,5-HT and DA in the hippocampal tissue of rats were detected by ELISA.The protein expression of BDNF and TrkB and the phosphorylation level of CREB in the hippocampal tissue were determined by Western blot.Results:Compared with the normal control group,the sugar water preference rate,autonomous activity score,levels of NE,5-HT,DA in hippocampal tissue,protein expression of BDNF and TrkB,and phosphorylation level of CREB in the model group were decreased,while the immobility time in water,levels of IL-6 and IL-1βin hippocampal tissue,and cell apoptosis rate were increased(P<0.05).The arrangement of neurons in the hippocampal tissue was loose and disordered,showed nuclear consolidation,and a large number of Nissl bodies were lost.Compared with the model group,the changes of the above indicators in the CBD-L group and the CBD-H group were opposite(P<0.05).K252a could weaken the improvement effect of CBD-H on depression behaviors in model rats(P<0.05).Conclusions:CBD could improve the depressive behavior in rats,which may be related to the activation of the BDNF/TrkB/CREB signaling pathway.
作者
陈婷婷
徐正清
苏邹
彭茜
魏欣洁
丁凡
CHEN Tingting;XU Zhengqing;SU Zou;PENG Qian;WEI Xinjie;DING Fan(Department of Pediatric Psychology,Wuhan Wudong Hospital,Wuhan 430040;Department of Substance Addiction,Wuhan Wudong Hospital,Wuhan 430040;Department of Medical Affairs Office,Wuhan Wudong Hospital,Wuhan 430040)
出处
《郑州大学学报(医学版)》
北大核心
2026年第2期142-147,共6页
Journal of Zhengzhou University(Medical Sciences)
关键词
大麻二酚
脑源性神经营养因子/酪氨酸激酶受体B/环磷酸腺苷反应元件结合蛋白信号通路
抑郁样行为
大鼠
cannabidiol
brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic adenosine monophosphate responsive element-binding protein signaling pathway
depressive like behavior
rat
