PPAR家族与运动能力研究进展

1.PPARs1990年,Issemann发现一种固醇类受体,它需要被脂肪酸类过氧化物酶增殖剂(peroxisomeproliferator)激活才能发挥作用,因此命名为过氧化物酶体增殖物激活受体(peroxisomeproliferator-activatedreceptor,PPARs)。PPARs属于核受体超基因家族成员,可调控多种核内基因的表达。由于其对耐力的调控作用而受到广泛关注。2.PPARs的生物学功能PPARs有3个亚基:PPARα、PPARβ(又称:PPARδ)和PPARγ。其功能是共同调节糖\脂代谢平衡,影响脑组织、骨组织、皮肤组织的生长与分化。PPARγ是这3个亚基中研究最热的,主要在脂肪存贮中…     

运动对肌纤维影响的细胞分子生物学研究

运用细胞分子生物学理论与方法，较系统地研究不同运动条件下肌纤维的膜受体、膜裁体、膜脂质，收缩装置、细胞骨架、相关基因及其表达调控，以及肌细胞凋亡的适应变化特征与机制，为运动医学增加新的内容，为体育科研提供新的视野。     

外泌体miRNAs——运动促进心血管健康的新靶点

运动可促进特定细胞来源外泌体（exosomes,EXO）的分泌,选择性地促进其内含miRNAs(exomiRs)的表达。exomiRs介导运动在抑制心血管细胞凋亡、炎症、纤维化、氧化应激,促进血管生成,提高心血管功能等方面发挥关键作用。exomiRs具有免于RNA酶分解的稳定性、预测心血管疾病的敏感性、载体低毒性等特征。测试特定exomiRs的表达有望成为心血管疾病临床预测、诊断以及评价运动康复效果的新方法。利用运动来源exomiRs进行异体注射或通过基因工程生产含特定exomiRs的纳米药物实施无细胞靶向治疗心血管疾病,具有很好的应用前景。     

肌组织特异性microRNA介导的骨骼肌衰减机制及运动的干预研究

目的探讨不同运动方式对肌肉特异性microRNA在骨骼肌中表达的影响及其与骨骼肌衰减的关系。方法 3月龄雄性C57BL/6小鼠36只,随机分为年轻组、老年组、抗阻训练老年组(尾部负重爬梯训练)、有氧训练老年组,每组9只。17个月饲养训练结束后,检测小鼠股四头肌湿质量(mg)与体质量(g)的比值(SI),用实时荧光定量RT-PCR法对miRNA-1、miRNA-133a/b、miRNA-206进行检测,同时检测IGF-1、PGC-1α、MAFbx及Myostatin等mRNA及蛋白的表达。结果发现老年鼠SI值显著下降,呈现肌肉流失征象,miR-1和miR-133a下调,IGF-1mRNA表达下调,而MAFbxmRNA表达上调,提示老年小鼠骨骼肌质量下降可能与IGF-1、MAFbx对骨骼肌蛋白质合成或降解的调控有关,推测miR-1和miR-133a参与了这一调控过程。而运动可显著增加老年鼠的SI值,延缓肌肉衰减,表现为运动训练的老年鼠其骨骼肌miR-1和miR-133a表达均有显著提高,IGF-1、PGC-1αmRNA表达上调,MAFbx及Myostatin mRNA表达也上调,但年龄因素或运动训练因素对所观测基因的蛋白表达影响均不如mRNA明显,且转录和翻译水平的调控亦未呈现一致性,反映出miRNA对基因调节作用的复杂性。结论长期有氧运动或抗阻运动可有效延缓肌肉流失,肌肉特异性microRNA可能通过对涉及肌再生或肌萎缩的关键基因IGF-1、PGC-1α、MAFbx转录后或翻译水平的调节而发挥重要作用。     

有氧运动通过心肌细胞吞运内皮细胞来源外泌体抑制细胞凋亡

目的:探讨运动干预对H9C2细胞内吞外泌体及抑制细胞凋亡的影响。方法:C57/BL6小鼠随机分为假手术组(S组)、心梗组(MI组)、心梗有氧运动组(ME组),每组8只,采用左冠状动脉前降支结扎术(left anterior descending of the coronary artery, LAD)制备MI模型,ME组手术结束1周后进行持续6周的有氧运动。训练结束后超声检测心脏LVIDs、LVIDd、FS和EF,Masson染色检测心肌纤维化;使用无外泌体培养基培养HUVEC细胞,并提取外泌体孵育H9C2细胞。使用AMPK激动剂(AICAR,2 mmol/L,24 h)、脂多糖(LPS,10μg/m L,4 h)干预H9C2细胞。NTA和Western Blotting鉴定、检测提取的外泌体;Hoechst 33342染色及TUNEL检测细胞凋亡水平;Western Blotting检测小鼠心肌及H9C2细胞中凋亡相关蛋白Bax、Bcl-2和cleaved-Caspase3。结果:与MI组比较,ME组心功能指标EF和FS显著增加(P<0.05),细胞凋亡蛋白Bax/Bcl-2,...     

运动对心肌细胞中凋亡调控基因表达的影响

目的：研究运动对心肌细胞中调控基因Bcl-2、Bax和P53的影响，以探讨凋亡调控基因对运动引起心肌细胞凋亡的作用。方法：以大鼠中等运动强度训练、一次性力竭运动和过度训练为运动模型，采用反转录聚合酶链式反应（RT—PCR）技术，观察了大鼠心肌细胞中调控基因Bcl-2、Bax和p53 mRNA的表达。结果：长期中等强度的运动可造成大鼠心肌细胞中凋亡调控基因Bcl-2 mRNA表达明显增加，可抑制心肌细胞凋亡；而力竭运动和过度训练可引起心肌细胞中Bcl-2 mRNA表达下降、调控基因Bax、P53 mRNA表达显著升高以及凋亡调控基因Bcl-2／Bax比值显著下降，可促进心肌细胞凋亡。结论：心肌细胞中凋亡调控基因Bcl-2、Bax和p53在不同运动后的不同表达，对心肌细胞凋亡的发生有明显的调控作用。     

低氧运动调节脂代谢的研究进展

低氧运动能更好的增加机体的能量消耗,促进脂肪酸β氧化(fatty acidβ-oxidation,FAO),调节胆固醇代谢,提供了更优越的脂代谢应激,降低体脂调节脂代谢。本文通过综述低氧运动对脂代谢的影响,探讨低氧运动调节脂代谢的分子机制及生理学意义,展望脂代谢的研究前景,旨为解决全球性超重与肥胖问题提供新的思路。     

茶多酚和运动对糖尿病脂代谢紊乱的影响

糖尿病不仅糖代谢异常变化,还常合并脂代谢紊乱。血脂异常与高血糖、高血压、肥胖等构成糖尿病慢性并发症的独立危险因素有关。脂代谢紊乱对糖尿病及其并发症的发生起着极其重要的作用。茶多酚对机体血脂代谢有正向调节作用具有降血脂功效。同时运动也可以有效的预防脂质代谢的紊乱。本文从茶多酚的降血脂功能和运动对糖尿病脂代谢的影响两方面评述两者对糖尿病治疗的机理,为茶多酚结合运动治疗糖尿病提供参考依据。     

细胞周期调控基因p21~(WAF1/CIP1)与肿瘤的关系

p21WAF1/C IP1基因是1993年发现并克隆的细胞周期依赖性蛋白激酶抑制因子(Cyc lin-dependent k inas inh ib itor,CD-K I)的家族成员,它参与细胞的多种功能活动。近年许多研究表明,p21WAF1/C IP1基因与肿瘤的发生、发展关系密切,从而引起学者的关注。1 p21WAF1/C IP1基因的发现     

网球运动调节脂代谢的FNDC5/Irisin途径研究

FNDC5/Irisin能够在运动的诱导下改善脂肪和糖代谢,参与白色脂肪的棕色化过程。本文重点阐述Irisin的释放及作用模式和受体的特点,总结了FNDC5/Irisin调控肥胖、葡萄糖稳态和影响运动的分子机制,为运动调节脂代谢提供参考依据。     

Refinement of saliva microRNA biomarkers for sports-related concussion

BackgroundRecognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.MethodsThis case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites. Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing. Within-subjects testing was used to identify and exclude miRNAs that changed with either (a) a single episode of exercise (166 samples from 83 individuals) or (b) season-long participation in contact sports (212 samples from 106 individuals). The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression (172 samples from 75 concussed and 97 non-concussed individuals).ResultsTwo miRNAs (miR-532-5p and miR-182-5p) decreased (adjusted p < 0.05) after a single episode of exercise, and 1 miRNA (miR-4510) increased only after contact sports participation. Twenty-three miRNAs changed at the end of a contact sports season. Two of these miRNAs (miR-26b-3p and miR-29c-3p) were associated (R > 0.50; adjusted p < 0.05) with the number of head impacts sustained in a single football practice. Among the 15 miRNAs not confounded by exercise or season-long contact sports participation, 11 demonstrated a significant difference (adjusted p < 0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (area under curve > 0.70) to identify concussion. A single ratio (miR-27a-5p/miR-30a-3p) displayed the highest accuracy (AUC = 0.810, sensitivity = 82.4%, specificity = 73.3%) for differentiating concussed and non-concussed participants. Accuracy did not differ between participants with SRC and non-SRC (z = 0.5, p = 0.60).ConclusionSalivary miRNA levels may accurately identify SRC when not confounded by exercise. Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive, sideline adjunct for SRC assessment.     

Exercise promotes angiogenesis by enhancing endothelial cell fatty acid utilization via liver-derived extracellular vesicle miR-122-5p

BackgroundAngiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects. Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs (miRNAs) after exercise and found that some of them act as exerkines. However, whether these extracellular vesicle miRNAs mediate the exercise-induced angiogenesis remains unknown.MethodsA 9-day treadmill training was used as an exercise model in C57BL/6 mice. Liver-specific adeno-associated virus 8 was used to knock down microRNA-122-5p (miR-122-5p). Human umbilical vein endothelial cells were used in vitro.ResultsAmong these differentially expressed extracellular vesicle miRNAs, miR-122-5p was identified as a potent pro-angiogenic factor that activated vascular endothelial growth factor signaling and promoted angiogenesis both in vivo and in vitro. Exercise increased circulating levels of miR-122-5p, which was produced mainly by the liver and shuttled by extracellular vesicles in mice. Inhibition of circulating miR-122-5p or liver-specific knockdown of miR-122-5p significantly abolished the exercise-induced pro-angiogenic effect in skeletal muscles, and exercise-improved muscle performance in mice. Mechanistically, miR-122-5p promoted angiogenesis through shifting substrate preference to fatty acids in endothelial cells, and miR-122-5p upregulated endothelial cell fatty-acid utilization by targeting 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT1). In addition, miR-122-5p increased capillary density in perilesional skin tissues and accelerated wound healing in mice.ConclusionThese findings demonstrated that exercise promotes angiogenesis through upregulation of liver-derived extracellular vesicle miR-122-5p, which enhances fatty acid utilization by targeting AGPAT1 in endothelial cells, highlighting the therapeutic potential of miR-122-5p in tissue repair.     

Effects of purposeful soccer heading on circulating small extracellular vesicle concentration and cargo

BackgroundConsidering the potential cumulative effects of repetitive head impact (HI) exposure, we need sensitive biomarkers to track short- and long-term effects. Circulating small extracellular vesicles (sEVs) (<200 nm) traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease. The purpose of this study was to identify the microRNA (miRNA) profile in circulating sEVs derived from human plasma following repetitive HI exposure.MethodsHealthy adult (aged 18–35 years) soccer players were randomly assigned to one of 3 groups: the HI group performed 10 standing headers, the leg impact group performed 10 soccer ball trapping maneuvers over 10 min, and the control group did not participate in any soccer drills. Plasma was collected before testing and 24 h afterward, and sEVs were isolated and characterized via nanoparticle tracking analysis. Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs, and candidate microRNAs were analyzed via quantitative polymerase chain reaction. In silico target prediction was performed using TargetScan (Version 7.0; targetscan.org) and miRWalk (http://mirwalk.umm.uni-heidelberg.de/) programs, and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney (HEK) 293T/17 cells.ResultsPlasma sEV concentration and size were not affected across time and group following repetitive HI exposure. After 24 h, the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p, miR-423-5p, and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p, miR-144-5p, miR-221-5p, and miR-22-3p. Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels. To our knowledge, miR-7844-5p is a previously unknown miRNA. We identified 8 miR-7844-5p mRNA targets: protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B), LIM and senescent cell antigen-like domains 1 (LIMS1), autophagy-related 12 (ATG12), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), integrin subunit alpha-1 (ITGA1), mitogen-activated protein kinase 1 (MAPK1), glycogen synthase kinase 3β (GSK3β), and mitogen-activated protein kinase 8 (MAPK8).ConclusionCollectively, these data indicate repetitive HI exposure alters plasma sEV miRNA content, but not sEV size or number. Furthermore, for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis, autophagy regulation, mood disorders, and neurodegenerative disease.     

ApoB、ApoE基因多态性与血脂异常的关系及运动训练的影响

载脂蛋白基因多态性与血脂异常的关系备受人们关注。综述了载脂蛋白B（ApoB）和载脂蛋白E（ApoE）基因多态性与血脂异常的关系、ApoE基因多态性时运动训练引起的血脂改善的影响方面的研究进展。ApoB基因Xbal、EcoRl多态性和ApoE多态性可能作为血脂增高的内在易感因素，在一定程度上影响体内脂质代谢；ApoE多态性影响血脂对运动训练的反应，且运动训练引起的血脂水平改变在不同基因型间存在种族和性别差异。     

游泳训练及联合补充线粒体营养素α-硫辛酸对wistar2型糖尿病大鼠血脂代谢及脂质过氧化水平的影响

目的:观察2型糖尿病(T2DM)模型大鼠,经8周游泳训练后,血脂代谢、血清氧化应激、血糖(FBG)、胰岛素敏感性(ISI)及肝脏组织二相酶活性变化,检测联合作用方式(游泳训练及联合补充α硫辛酸)对wistarT2DM大鼠血脂代谢及脂质过氧化水平的影响,并探讨其内在影响机制。方法:实验材料wistar大鼠60只,造模完成后随机分成4组,对照组(CON);α硫辛酸(LA);游泳运动组(SEX);α硫辛酸+游泳运动组(LA+SEX),每组15只。进行游泳训练共计8周,观察各组大鼠血脂代谢水平、FBG、ISI及肝脏组织二相酶活性变化。结果:经联合作用方式可极显著性降低wistar大鼠血清总胆固醇和甘油三酯水平,降低LDL-C含量和FFA水平,提高HDL-C;在降低FBG,提高ISI作用上存在叠加效应(P<0.01),对胰岛素水平无显著性影响;在改善血清氧化应激水平作用上(降低ROS和提高SOD),存在增强作用(P<0.01);对肝脏组织二相酶的影响,在对谷胱甘肽-S-转移酶(GST)和谷胱甘肽过氧化物酶(GPX)存在增强作用,对醌氧化还原酶1(NQO-1)则无此作用。结论:联合作用方式可以有效降低血清及肝脏脂质过氧化水平,纠正血脂代谢异常,提高ISI。其保护作用可能是通过降低机体氧化应激水平,维持机体血脂正常代谢水平,减少氧化应激而实现。提示,联合作用方式可以为治疗T2DM提供新思路。     

改善单纯性肥胖儿童血压血脂水平的运动处方研究

对20名单纯性肥胖儿童进行了血压、血脂(TC：用酶反应试剂药盒测定，TG：乙酰丙酮微量测定法)检测，并对10名儿童进行了8周的耐力训练(训练中未对受试者提出低盐、低脂的饮食要求)。结果表明：8周的耐力训练后，肥胖儿童血清中血脂(TG)含量下降，HDL—C显著上升，血脂代谢紊乱得到缓解，同时血压有明显下降。从众多因素的分析中发现，TG与SBP(r=0．32)、DBP(r=0．22)呈正相关，而ApoAI与SBP(r=-0．19)、DBP(r=-0．20)呈负相关，提示单纯性肥胖儿童的高血压与其血脂代谢紊乱有关。非饮食干预条件下的耐力训练有助于降低肥胖儿童的血压、血脂。     

AMPK与2型糖尿病的关系及其在运动介导下的研究

腺苷酸活化蛋白激酶（AMPK）是一种重要的蛋白激酶,其主要作用是协调代谢和能量平衡。AMPK被激活后在增加骨骼肌对葡萄糖摄取、增强胰岛素敏感性方面发挥重要作用。由于在调节糖代谢方面的作用,AMPK为治疗胰岛素抵抗和2型糖尿病提供了新的药理靶点。     

运动对ApoE基因敲除鼠动脉粥样硬化形成的干预作用及机制

探讨运动对动脉粥样硬化形成的延缓作用及抗氧化作用途径、脂代谢途径,以ApoE建立动脉粥样硬化(AS)模型,观察有氧运动对ApoE-/-小鼠主动脉斑块面积、血脂、血氧化低密度脂蛋白、肝MDA、肝SOD的影响。结果:ApoE-/-小鼠形成明显斑块,存在氧化水平的升高和血脂紊乱,运动可使斑块面积减少,使ApoE-/-小鼠血oxldl、肝MDA降低,肝SOD升高,但运动没有影响ApoE-/-小鼠的血脂水平,且运动均不影响正常状态,即C57小鼠的脂代谢和氧化水平。结论:运动可通过调节机体的氧化抗氧化水平,发挥抗动脉粥样硬化的作用,可能独立于降血脂途径。     

有氧运动与营养干预对防治糖尿病的实验研究

糖尿病是一种严重危害人类生命和健康的常见慢性疾病，被称为现代疾病中的“第二杀手”，对人体的危害仅次于癌症。本文通过有氧运动结合葛根素的干预，观察糖尿病大鼠的糖、脂代谢的变化。结果表明，有氧运动与葛根素干预后，糖尿病大鼠的高脂、高糖的现象得到了较好的控制，高脂、高糖的水平也恢复到接近正常水平。本文提示，通过有氧运动与葛根素的干预能在一定程度防治糖尿病的发生。