槲皮素治疗联合运动训练对脑卒中后大鼠抑郁样行为影响的研究

The effects of quercetin treatment combined with exercise training on post-stroke depression like behavior in rats

目的:探讨槲皮素治疗联合运动训练对脑卒中模型大鼠抑郁样行为的治疗作用。方法:将50只大鼠随机分为假手术组(sham)、卒中抑郁组(PSD)、槲皮素组(QUE)、运动组(EXE)和槲皮素+运动组(QUE+EXE)。通过大脑中动脉闭塞(MCAO)技术制备大鼠卒中后抑郁模型。通过悬尾实验(TST)和糖水偏爱实验(SPT)来评估各组大鼠抑郁样行为;利用酶联免疫吸附试验(ELISA)检测各组大鼠血清和前额叶皮质中肿瘤坏死因子α(TNF-a)和白细胞介素1-β(IL-1β)的含量;利用Western Blot检测各组大鼠前额叶皮质中脑源性神经生长因子(BDNF)、原肌球蛋白受体激酶B (Trk-B)、糖原合成酶激酶-3β(GSK-3β)和β-连环蛋白(β-catenin)的表达。结果:行为学检测结果显示PSD组大鼠不动的时间显著增加(P<0.05),同时糖水摄入量及糖水偏爱百分比均显著下降(P<0.05),而槲皮素和运动训练均逆转了这些行为(P<0.05)。ELISA检测显示PSD组大鼠血清及前额叶皮质中TNF-α和IL-1β表达升高(P<0.05),而槲皮素和运动训练均不同程度使其表达降低(P<0.05)。Western Blot检测显示PSD组前额叶皮质中BDNF、Trk-B和β-catenin的蛋白表达下降(P<0.05),GSK-3β表达升高(P<0.05),而槲皮素和运动训练均上调了脑卒中模型大鼠前额叶组织中BDNF、Trk-B和β-catenin的表达(P<0.05)。结论:运动训练改善了MCAO诱导的大鼠卒中后抑郁样行为,槲皮素治疗联合运动训练可能通过抑制脑卒中模型大鼠前额叶皮质中的炎症因子并上调BDNF/Trk-B/β-catenin系统发挥抗抑郁作用。

Objective: To evaluate the therapeutic effect of quercetin treatment combined with exercise training on post-stroke depression like behavior in rats. Methods: Fifty rats were randomly divided into sham group(sham), post stroke depression(PSD), quercetin group(QUE), exercise group(EXE), and quercetin+exercise group(QUE+EXE). A rat model of PSD was established by middle cerebral artery occlusion(MCAO). The depression like behavior of rats in each group was evaluated by tail suspension test(TST) and sugar water preference test(SPT). ELISA was used to detect the levels of inflammatory cytokines TNF-α and IL-1β in serum and prefrontal brain tissue of each group. Western Blot was used to determine the protein expression of BDNF, Trk-B, GSK-3β, and β-catenin in the prefrontal cortex of each group. Results: The results of behavioral test showed that the immobility time of PSD group rats increased significantly(P<0.05), and the sugar water intake and the percentage of sugar water preference decreased significantly(P<0.05), while quercetin and exercise training reversed these behaviors(P<0.05). ELISA showed TNF-a and IL-1β in serum and prefrontal cortex of PSD group increased(P<0.05). While quercetin and exercise training decreased its expression in different degrees(P<0.05). Western Blot showed that the protein expression of BDNF, Trk-B, and β-catenin in the prefrontal cortex decreased in PSD group(P<0.05), the protein expression of GSK-3β increased(P<0.05). While quercetin and exercise training increased the protein expression of BDNF, Trk-B, and β-catenin in the prefrontal cortex of PSD models in rats(P<0.05). Conclusion: Exercise training improved post-stroke depression like behavior induced by MCAO in rats, quercetin treatment combined with exercise training may play an antidepressant role by inhibiting inflammatory factors in the prefrontal cortex of PSD models rat and upping regulate of pathway of BDNF/Trk-B/β-catenin system.