低氧训练对肥胖大鼠大脑皮质脑源性神经营养因子及酪氨酸激酶受体B的调节作用

Regulation of Hypoxia Training on BDNF and TrkB in Cerebral Cortex of Obese Rats

目的:通过高脂饮食喂养建立肥胖大鼠模型,探讨低氧训练对肥胖大鼠大脑皮质脑源性神经营养因子(BDNF)及其受体酪氨酸激酶受体B(TrkB)的影响,为低氧训练改善肥胖大鼠神经系统功能提供理论依据。方法:32只3周龄雄性SD大鼠,高脂饲料喂养10周建立肥胖模型,随机分为常氧安静组(NC组)、常氧训练组(NT组)、低氧安静组(HC组)、低氧训练组(HT组)。NC组和NT组统称为常氧组(N组),HC组和HT组统称为低氧组(H组),NC组和HC组统称为安静组(C组),NT组和HT组统称为训练组(T组)。低氧环境氧气浓度为13.6%,训练组用水平动物跑台进行耐力训练,常氧组训练强度为25 m/min,低氧组训练强度为20 m/min,持续运动1 h/天、5天/周,共4周。应用RT-qPCR检测各组大鼠大脑皮质BDNF、TrkB mRNA表达水平;应用Western-Blot检测大鼠大脑皮质BDNF、TrkB蛋白以及磷酸化TrkB蛋白(p-TrkB)的表达;应用ELISA检测大鼠大脑皮质肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的水平。结果:1)T组大鼠大脑皮质BDNF和TrkB m RNA表达较C组显著上升(P<0.01),H组较N组显著上升(P<0.05),NT组较NC组显著上升(P<0.01),HT组较HC组和NT组显著上升(P<0.01);2)T组大脑皮质BDNF蛋白表达较C组显著上升(P<0.01),H组和N组无显著性差异;各组大鼠大脑皮质TrkB蛋白表达水平无显著差异;T组p-TrkB蛋白表达较C组显著上升(P<0.01),H组和N组无显著性差异;3)T组TNF-α、IL-1β和IL-6表达较C组显著下降(P<0.05),H组和N组无显著性差异。结论:运动训练能减少肥胖大鼠大脑皮质炎症因子TNF-α、IL-1β和IL-6的分泌,促进大脑皮质BDNF及其受体TrkB的表达,从而提高神经营养作用。低氧训练在提高肥胖大鼠大脑皮质BDNF和TrkB m RNA的表达上较常氧训练更具优势。

Objective To explore the effect of hypoxia training on brain derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)in the cerebral cortex of obese rats,so as to provide theoretical basis for hypoxia training to improve the nervous system function.Methods Thirty-two 3-week male Sprague-Dawley rats were induced obesity model by feeding high-fat diet for 10 weeks.Then they were randomly divided into a normal oxygen control(NC)group,a normal oxygen training(NT)group,a hypoxic control(HC)group and a hypoxic training(HT)group.NC and NT groups were called normoxia(N)group,HC and HT were called hypoxia(H)group,NC and HC were called quiet(C)group,and NT and HT were called training(T)group.For H groups,they were kept in the hypoxic environment with the oxygen concentration of 13.6%,while for T groups,rats underwent 1-hour treadmill running 5 days per week for 4 weeks at a speed of 25 m/min in NT group and 20 m/min in HT group.After the intervention,the expressions of BDNF and TrkB m RNA were detected using the real-time quantitative polymerase chain reaction,the expressions of BDNF,TrkB and p-TrkB protein were measured using Western blotting,while the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were evaluated using enzyme-linked immunosorbent assay.Results The average expression of BDNF and TrkB m RNA in group T,H,NT and HT were significantly higher than group C,N,NC as well as HC and NT correspondingly(P<0.01).The average BDNF protein expression of group T was significantly higher than group C(P<0.01),but there was no significant difference between group H and group N.No significant differences were found in the average TrkB protein expression among different groups.However,the average expression of p-TrkB of the group T was significantly higher than the group C(P<0.01).The average TNF-α,IL-1βand IL-6 expression of group T were significantly lower than group C(P<0.05).Conclusion Training can reduce the secretion of inflammatory factors such as TNF-α,IL-1βand IL-6 and promote the expression of BDNF and TrkB in the cerebral cortex of obese rats,which can increase neurotrophy.Hypoxia training is superior to normal oxygen training in improving the expression of BDNF and TrkB m RNA in the cerebral cortex of obese rats.