| 3 | 0 | 6 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨耐力运动和抗阻运动后大鼠脑内β-羟基丁酸水平的变化，以及β-羟基丁酸调节大鼠大脑内脑源性神经营养因子（BDNF）水平的作用和机制。方法 将30只SD雄性大鼠随机分为对照组（n=10）、跑台运动组（n=10）和爬梯运动组（n=10）。对照组不做任何运动，跑台运动组和爬梯运动组根据经典的耐力和抗阻运动模型运动8周。运动干预后，取大鼠尾静脉血、脑组织和肱三头肌组织，进行液氮冻存和多聚甲醛固定。测量大鼠体重、血清睾酮水平。光学显微镜下观察骨骼肌纤维横截面积。采用ELISA和Western blot方法测定BDNF、β-羟基丁酸、沉默信息调节因子1(SIRT 1)、过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)水平。通过RT-PCR检测组蛋白去乙酰化酶3(HDAC3)的表达。结果 8周运动干预后，各组大鼠的体重均明显增加，但跑台运动组大鼠的体重低于对照组（P<0.01）。8周跑台运动和爬梯运动均引起骨骼肌纤维横截面积增加，其中爬梯运动组的骨骼肌纤维横截面积增加更为明显（P<0.001）。8周跑台运动后，大鼠大脑内的BDNF水平和β-羟基丁酸水平均明显高于对照组（P<0.05）,HDAC3的表达明显下降（P<0.001）。8周爬梯训练未引起大鼠大脑内BDNF水平增加，大脑中β-羟基丁酸水平显著降低（P<0.001）,SIRT 1及PGC-1α水平也明显下降（P<0.01），而HDAC3表达未出现明显变化。结论 脂肪酸代谢产物β-羟基丁酸水平在不同运动方式引起的BDNF水平变化中起关键作用，可通过不同的表观遗传机制调控大脑BDNF水平。
Abstract：Objective To explore the changes in β-hydroxybutyrate levels in rat brains after endurance and resistance exercises,as well as its role and mechanism in regulating the levels of Brain-Derived Neurotrophic Factor(BDNF) in the rat brain.Methods Thirty Sprague-Dawley(SD) rats were randomly divided into a control group(n =10),a treadmill exercise group(n =10),and a ladder-climbing exercise group(n =10).The control group did not do any exercise,while the treadmill group and ladder-climbing group exercised for 8 weeks according to the reported endurance and resistance exercise model.After the exercise intervention,the tail vein blood,brain tissue,and triceps brachii muscle tissue of the rats were collected,and the tissues were frozen in liquid nitrogen and fixed in paraformaldehyde.Record the weight and training load of rats.Cross-sectional area(CSA) was quantified.The levels of BDNF,β-hydroxybutyrate,silence infor-mation regulator 1(SIRT 1),and PGC-1α were measured by ELISA or/and Western blot,and the expression of histone deacetylase 3(HDAC3) was detected by RT-PCR.Results After 8 weeks,the body weight of rats in each group increased significantly,but the body weight of rats in the treadmill group was significantly lower than that of the control group(P <0.01).Both treadmill exercise and ladder-climbing exercise for 8 weeks caused an increase in the CSA of skeletal muscle,but the increase in CSA was more pronounced in the ladderclimbing exercise group(P <0.001).After 8 weeks of treadmill exercise,the BDNF level in the rat brain was significantly higher than that in the control group(P <0.05).At the same time,the level of fatty acid metabolite β-hydroxybutyrate in the brain increased significantly(P <0.05),and the expression of HDAC3 decreased significantly(P <0.001);In contrast,8 weeks of ladder-climbing training did not cause a significant increase in BDNF levels,a significant decrease in β-hydroxybutyrate(P <0.001),in the expression of SIRT 1 and PGC-1α in the brain were observed(P <0.01),and no significant change in the expression of HDAC3 was found.Conclusion The level of fatty acid metabolite β-hydroxybutyrate plays a key role in the regulation of BDNF levels caused by different exercise modes through different epigenetic mechanisms.
[1] Yin Y, Liu J, Fan Q, et al. Long-term spaceflight composite stress induces depression and cognitive impairment in astronauts-insights from neuroplasticity[J]. Translational Psychiatry, 2023, 13(1):342.
[2] Clement G, Ngo-Anh JT. Space physiology II:adaptation of the central nervous system to space flight-past, current, and future studies[J].European Journal of Applied Physiology , 2013, 113(7):1655-1672.
[3] Jiao SS, Shen LL, Zhu C, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease[J].Translational Psychiatry, 2016, 6(10):e907.
[4] Duman RS, Deyama S, Foga?a MV. Role of BDNF in the pathophysiology and treatment of depression:Activity-dependent effects distinguish rapid-acting antidepressants[J]. European Journal of Neuroscience,2021, 53(1):126-139.
[5] Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders[J]. Biological Psychiatry, 2006, 59(12):1116-1127.
[6] Walsh EI, Smith L, Northey J, et al. Towards an understanding of the physical activity-BDNF-cognition triumvirate:a review of associations and dosage[J]. Ageing Research Reviews, 2020, 60:101044.
[7] Lippi G, Mattiuzzi C, Sanchis-Gomar F. Updated overview on interplay between physical exercise, neurotrophins, and cognitive function in humans[J]. Journal of Sport and Health Science , 2020, 9(1):74-81.
[8] Dinoff A, Herrmann N, Swardfager W, et al. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults:a meta-analysis[J]. European Journal of Neuroscience , 2017,46(1):1635-1646.
[9] Coelho FG, Vital TM, Stein AM, et al. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease[J]. Journal of Alzheimer's Disease, 2014, 39(2):401-408.
[10] El-Sayes J, Harasym D, Turco CV, et al. Exercise-induced neuroplasticity:a mechanistic model and prospects for promoting plasticity[J]. Neuroscientist,2019, 25(1):65-85.
[11] Wang YH, Zhou HH, Luo Q, et al. The effect of physical exercise on circulating brain-derived neurotrophic factor in healthy subjects:a meta-analysis of randomized controlled trials[J]. Brain and Behavior,2022, 12(4):e2544.
[12] Goekint M, de Pauw K, Roelands B, et al. Strength training does not influence serum brain-derived neurotrophic factor[J]. European Journal of Applied Physiology, 2010, 110(2):285-293.
[13] Murawska-Cialowicz E, de Assis GG, Clemente FM, et al. Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test[J]. Scientific Reports , 2021, 11(1):8599.
[14] Huang T, Larsen KT, Ried-Larsen M, et al. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans:a review[J]. Scandinavian Journal of Medicine&Science in Sports , 2014, 24(1):1-10.
[15] Shimazu T, Hirschey MD, Newman J, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor[J]. Science, 2013, 339(6116):211-214.
[16] Newman JC, Verdin E. Beta-Hydroxybutyrate:a Signaling Metabolite[J]. Annual Review of Nutrition, 2017, 37:51-76.
[17] D'mello SR. Histone deacetylase-3:friend and foe of the brain[J].Experimental Biology and Medicine(Maywood), 2020, 245(13):1130-1141.
[18] Juan CG, Matchett KB, Davison GW. A systematic review and meta-analysis of the SIRT 1 response to exercise[J]. Scientific Reports , 2023,13(1):14752.
[19] Lee S, Barton ER, Sweeney HL, et al. Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats[J]. Journal of Applied Physiology(1985), 2004, 96(3):1097-1104.
[20] Neves RV, Souza MK, Passos CS, et al. Resistance training in spontaneously hypertensive rats with severe hypertension[J]. Arquivos Brasileiros de Cardiologia , 2016, 106(3):201-209.
[21] Hornberger TA Jr., Farrar RP. Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat[J].Journal of Applied Physiology, 2004, 29(1):16-31.
[22] Loehr JA, Guilliams ME, Petersen N, et al. Physical training for long-duration spaceflight[J]. Aerospace Medicine and Human Performance , 2015, 86(12 Suppl):14-23.
[23] Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation[J]. Cell Metabolism , 2013, 17(2):162-184.
[24] Kwak SE, Bae JH, Lee JH, et al. Effects of exercise-induced beta-hydroxybutyrate on muscle function and cognitive function[J]. Physiological Reports , 2021, 9(3):e14497.
[25] Hong S, Zhou W, Fang B, et al. Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion[J]. Nature Medicine ,2017, 23(2):223-234.
[26] Gong Y, Cao R, Ding G, et al. Integrated omics approaches to characterize a nuclear receptor corepressor-associated histone deacetylase in mouse skeletal muscle[J]. Molecular And Cellular Endocrinology, 2018, 471:22-32.
[27] Yan X, Qu X, Tian R, et al. Hypoxia-induced NAD+interventions promote tumor survival and metastasis by regulating mitochondrial dynamics[J]. Life Sciences, 2020, 259:118171.
[28] Qiu X, Lu P, Zeng X, et al. Study on the mechanism for SIRT 1 during the process of exercise improving depression[J]. Brain Sciences, 2023,13(5):719.
[29] Dabke P, Das AM. Mechanism of action of ketogenic diet treatment:impact of decanoic acid and beta-hydroxybutyrate on sirtuins and energy metabolism in hippocampal murine neurons[J]. Nutrients, 2020,12(8):2379.
基本信息:
DOI：10.16289/j.cnki.1002-0837.2025.05005
中图分类号:R852.22
引用信息:
[1]于涛,房国梁,李鹏飞,等.β-羟基丁酸在不同运动调控大脑BDNF水平中的作用[J].航天医学与医学工程,2025,36(05):416-422.DOI:10.16289/j.cnki.1002-0837.2025.05005.
基金信息: