摘要
目的探讨柴胡加龙骨牡蛎汤(CLM)对肿瘤后抑郁模型大鼠海马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(BDNF/TrkB/CREB)信号通路的影响。方法采用接种腹水癌细胞系S180细胞建立肿瘤大鼠模型,再通过慢性不可预知温和刺激(CUMS)诱导肿瘤后抑郁大鼠模型。将12只模型大鼠分为模型对照组、CLM组(每10 g体质量给药0.1 mL),各6只;另设正常对照组(6只)。采用旷场实验(OFT)、悬尾实验(TST)、强迫游泳实验(FST)检测大鼠的抑郁样行为,酶联免疫吸附试验(ELISA)试剂盒检测大鼠血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,以及海马组织白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)与IL-10的水平,免疫印迹(Western blot)法检测BDNF,TrkB,CREB及磷酸化环腺苷酸应答元件结合蛋白(p-CREB)的水平。结果与模型对照组比较,CLM组大鼠OFT距离、时间及TST,FST静止时间均显著减少(P<0.01),血清SOD和GSH-Px水平均显著升高(P<0.01),海马组织中IL-1β和TNF-α水平均显著升高(P<0.01),IL-10水平显著降低(P<0.01),BDNF和TrkB蛋白表达及p-CREB/CREB均显著上调(P<0.01)。结论CLM可显著改善肿瘤后抑郁模型大鼠的抑郁样行为,抑制海马神经炎性反应,可能与上调BDNF/TrkB/CREB信号通路有关。
Objective To investigate the effect of Chaihujialonggumuli Decoction(CLM)on brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic adenosine monophosphate response element-binding protein(BDNF/TrkB/CREB)signaling pathway in hippocampus of model rats with post-tumor depression.Methods The tumor rat models were established by inoculating ascites cancer cell line S180 cells,and then induced to post-tumor depression rat model by chronic unpredictable mild stimulation(CUMS).Twelve model rats were divided into the model group and the CLM group(rats were administered 0.1 mL of CLM per 10 g),with six rats in each group,and the normal control group(six rats)was also set.Open field test(OFT),tail suspension test(TST),and forced swimming test(FST)were used to detect depression-like behavior in rats.Enzyme-linked immunosorbent assay(ELISA)kit was used to detect the levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in serum,the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and IL-10 in the hippocampal tissue.Western blot was used to detect the levels of BDNF,TrkB,CREB,and phosphorylated cyclic adenosine monophosphate response element-binding protein(p-CREB).Results Compared with those in the model group,the distance and time of rats in OFT,the immobility time of rats in TST and FST in the CLM group significantly decreased(P<0.01),the levels of serum SOD and GSH-Px in the CLM group significantly increased(P<0.01),the levels of IL-1βand TNF-αin the hippocampal tissue in the CLM group significantly increased(P<0.01),the levels of IL-10 in the hippocampal tissue in the CLM group significantly decreased(P<0.01),while the protein expression of BDNF and TrkB,and the p-CREB/CREB in the hippocampal tissue in the CLM group significantly up-regulated(P<0.01).Conclusion CLM can significantly improve depression-like behavior in post-tumor depression model rats,inhibit hippocampal neuroinflammatory response,and may be related to up-regulating the BDNF/TrkB/CREB signaling pathway.
作者
周振伟
董燕玲
杨文轩
安颖奇
张朝永
徐莹
段铮
刘子琳
郑红刚
王清贤
ZHOU Zhenwei;DONG Yanling;YANG Wenxuan;AN Yingqi;ZHANG Chaoyong;XU Ying;DUAN Zheng;LIU Zilin;ZHENG Honggang;WANG Qingxian(Tangshan Fifth Hospital,Tangshan,Hebei,China 063000)
出处
《中国药业》
CAS
2023年第17期29-34,共6页
China Pharmaceuticals
基金
河北省中医药管理局中医药类科研计划课题[2018325]。
关键词
肿瘤后抑郁
柴胡加龙骨牡蛎汤
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
作用机制
post-tumor depression
Chaihujialonggumuli Decoction
brain-derived neurotrophic factor
tyrosine kinase receptor B
cyclic adenosine monophosphate response element-binding protein
mechanism of action
