基于BDNF通路探讨樱桃叶水煎液对CUMS大鼠的抗抑郁作用机制

Exploring Antidepressant Mechanism of Cherry Leaves Decoction on CUMS Rats Based on BDNF Pathway

目的探讨樱桃叶水煎液对慢性不可预知性温和应激(CUMS)模型大鼠的抗抑郁作用及可能机制。方法将雄性Sprague-Dawley(SD)大鼠随机分为空白组、CUMS模型组、盐酸氟西汀组(2 mg·kg^(-1))以及樱桃叶水煎液低、中、高剂量组(1.8、2.7、3.6 g·kg^(-1))。复制CUMS模型,采用强迫游泳实验、悬尾实验和糖水偏好实验观察大鼠行为学变化;酶联免疫吸附实验(ELISA)测定大鼠血清促肾上腺皮质激素(ACTH)含量;Western Blot法测定大鼠海马组织中脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)、Ras相关C3肉毒杆菌毒素底物1(Rac1)、LIM激酶1(LIMK1)、丝切蛋白(cofilin)的表达水平。结果(1)与空白组比较,CUMS模型组大鼠强迫游泳实验和悬尾实验的不动时间增加(P<0.01),糖水偏好系数下降(P<0.01);血清ACTH水平上调(P<0.01);海马组织BDNF、TrkB、Rac1、LIMK1、cofilin蛋白表达降低(P<0.01)。(2)与CUMS模型组比较,樱桃叶水煎液干预后大鼠强迫游泳实验和悬尾实验的不动时间减少(P<0.05,P<0.01),而糖水偏好系数上升(P<0.01);血清ACTH水平下降(P<0.01);海马组织BDNF、TrkB、Rac1、LIMK1、cofilin蛋白表达增强(P<0.05,P<0.01)。结论樱桃叶水煎液具有一定的抗抑郁作用,其机制可能与调节BDNF/TrkB及其下游的Rac1/LIMK1/cofilin信号通路有关。

ObjectiveTo explore the antidepressant effect and possible mechanism of cherry leaves decoction on rats with chronic unpredictable mild stress(CUMS).MethodsMale Sprague-Dawley rats were randomly divided into blank group,CUMS group,fluoxetine hydrochloride group(2 mg·kg^(-1)),cherry leaves decoction low-,medium-,and high-dose groups(1.8,2.7 and 3.6 g·kg^(-1),respectively). The CUMS model was established and the depression status of rats was evaluated by forced swimming test,tail suspension test and taste preference test. The content of adrenocorticotropic hormone(ACTH) in serum was detected by enzyme linked immunosorbent assay(ELISA).Western Blot was used to determine the protein expression levels of BDNF,TrkB,Rac1,LIMK1 and cofilin in rat hippocampus.Results(1) Compared with the control group, the immobility time of forced swimming and tail suspension was increased in the CUMS group(P<0.01),while the sugar water preference coefficient was decreased(P<0.01). Moreover, the serum ACTH level was increased(P<0.01) and the expressions of BDNF, TrkB,Rac1,LIMK1,and cofilin in the hippocampal were decreased(P<0.01).(2)Compared with the CUMS group,the immobility time was reduced(P<0.05,P<0.01),while the sugar water preference coefficient was increased(P<0.01). In additional, the serum ACTH level was decreased(P<0.01), and the expressions of BDNF, TrkB,Rac1, LIMK1, and cofilin protein in hippocampus were increased(P<0.05, P<0.01) after the intervention of cherry leaves decoction.ConclusionCherry leaves decoction has a modest antidepressant effect,and the mechanism of antidepression may be related to the regulation of BDNF/TrkB and its downstream Rac1/LIMK1/cofilin signaling pathway.