机构地区:[1]湖南中医药大学临床医学院,长沙410208 [2]湖南省脑科医院精神科,长沙410007
出 处:《中国医师杂志》2023年第12期1794-1799,共6页Journal of Chinese Physician
基 金:湖南省临床医学研究中心(2021SK4022);湖南省重点研发项目(2020SK2123);湖南省卫生计生委科研课题(202103090662,202203094023)。
摘 要:目的研究川金解郁汤对慢性不可预知性应激(CUMS)诱导的抑郁大鼠模型的神经保护作用。方法48只成年雄性健康SD大鼠,随机选取12只为对照组,其余大鼠建立CUMS抑郁模型。将建模成功后的大鼠随机分成3组:CUMS组、氟西汀组和川金解郁汤组;分别给予0.9%氯化钠溶液氟西汀、川金解郁汤干预4周。造模后、干预后通过旷场实验、糖水偏爱实验,测定大鼠抑郁水平;干预后采用实时荧光定量PCR(qRT-PCR)检测脑源性神经营养因子(BDNF)、酪氨酸蛋白激酶受体B(TrkB)、环磷酸腺苷反应元件结合蛋白(CREB)mRNA在海马齿状回的表达量,免疫荧光检测BDNF与神经元核心抗原(NeuN)的表达量,蛋白免疫印迹法(Western blot)检测胶质纤维酸性蛋白(GFAP)水平。结果造模后,CUMS组、氟西汀组、川金解郁汤组的糖水消耗、糖水偏爱、垂直运动及水平运动结果明显低于对照组(均P<0.01);干预后,CUMS组以上指标低于对照组(均P<0.01),氟西汀组与川金解郁汤组以上指标均高于CUMS组(P<0.01或P<0.05),但低于对照组(P<0.01或P<0.05)。qRT-PCR结果显示,CUMS组、氟西汀组、川金解郁汤组的BDNF、TrkB、CREB mRNA表达量均明显低于对照组(均P<0.01);氟西汀组与川金解郁汤组的上述指标均显著高于CUMS组(均P<0.01)。免疫荧光结果显示,CUMS组的BDNF、NeuN表达量均显著低于对照组(均P<0.01);氟西汀组、川金解郁汤组以上指标均高于CUMS组(P<0.01或P<0.05),且川金解郁汤组所有指标及氟西汀组NeuN表达量低于对照组(P<0.01或P<0.05)。Western blot结果显示,CUMS组的GFAP蛋白表达低于对照组(P<0.01);氟西汀组GFAP蛋白表达高于CUMS组(P<0.05)。结论川金解郁汤可改善大鼠抑郁行为学指标,提高海马齿状回BDNF、TrkB、CREB及NeuN表达,提示川金解郁汤可能通过BDNF/TrkB/CREB通路发挥神经保护作用。Objective To study the neuroprotective effect of Chuanjin Jieyu decoction on a chronic unpredictable stress(CUMS)induced depression rat model.Methods A total of 48 adult male healthy Sprague-Dawley(SD)rats were randomly selected,with 12 rats as the control group,and the remaining rats were used to establish a CUMS depression model.After successful modeling,the rats were randomly divided into three groups:CUMS group,fluoxetine group,and Chuanjin Jieyu decoction group;0.9%sodium chloride solution fluoxetine and Chuanjin Jieyu decoction were respectively administered for intervention for 4 weeks.After modeling and intervention,depression levels in rats were measured through open field experiments and sugar water preference experiments;After intervention,real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression levels of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase receptor B(TrkB),and cyclic adenosine monophosphate responsive element binding protein(CREB)mRNA in the dentate gyrus of the hippocampus.Immunofluorescence was used to detect the expression levels of BDNF and NeuN.Western blot was used to detect the level of glial fibrillary acidic protein(GFAP).Results After modeling,the sugar consumption,sugar preference,vertical and horizontal movement results of the CUMS group,fluoxetine group,and Chuanjin Jieyu decoction group were significantly lower than those of the control group(all P<0.01);After intervention,the above indicators in the CUMS group were lower than those in the control group(all P<0.01).The above indicators in the fluoxetine group and the Chuanjin Jieyu decoction group were higher than those in the CUMS group(P<0.01 or P<0.05),but lower than those in the control group(P<0.01 or P<0.05).The qRT-PCR results showed that the mRNA expression levels of BDNF,TrkB,and CREB in the CUMS group,the fluoxetine group,and the Chuanjin Jieyu decoction group were significantly lower than those in the control group(all P<0.01);The above indicators in th
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