运动训练对核转录因子kappaB信号通路及炎性基因影响的研究进展

NF-κB(核转录因子-kappaB)信号通路在机体的免疫应答、细胞增殖、凋亡和生长发育中发挥重要作用。运动训练过程中机体产生的活性氧以及运动性肌肉损伤激活了NF-κB信号通路,对NF-κB活性的影响与运动训练的持续时间、频率和强度有关。急性剧烈运动导致了NF-κB活性一过性提高;长期有规律的运动训练能够降低由于衰老和慢性炎症反应而上调的NF-κB的活性;长期剧烈的运动训练导致了NF-κB的慢性持续激活,使通路上各指标的表达发生变化,细胞核中聚集NF-κB的亚基p65浓度增多,转录靶基因,从而使炎性基因的表达大幅度升高,一方面放大机体固有免疫系统对抗运动性应激,另一方面参与了骨骼肌运动性慢性炎症的形成。     

mTOR信号传导通路及运动对其影响的分子机制综述

从mTOR的分子结构着手,综述了以mTOR为中心的4条信号传导通路(2条mTOR上游信号通路、2条mTOR下游信号通路).这些信号通路在运动影响骨骼肌的信号传导过程当中发挥着举足轻重的作用.所有这些引起骨骼肌质量变化的信号系统,都是以mTOR为中心的.交互联系,构成一个统一的信号传导网络.一方面,运动引起骨骼肌肥大受到PI3K/Akt/mTOR和PI3K/Akt/TSC12/mTOR两条通路影响;另一方面,运动引起骨骼肌萎缩受到AMPK/TSC2/mTOR信号传导通路影响.     

PGC-1a适应骨骼肌不同持续时间与强度收缩活动的研究进展

本综述通过对PGC-1α依赖性信号传导的研究，描述不同持续时间、强度和模式的有氧运动，对调节骨骼肌线粒体生物合成的分子事件的影响。这对于治疗各种代谢性疾病以及优化运动训练计划至关重要。现有研究表明，30-90min的有氧运动无法提供额外的刺激来激活信号通路，以调节PGC-1α的翻译后修饰以及PPARGC1A的基因表达。而II型肌纤维募集的增加，导致运动强度显著影响线粒体的生物合成并伴随着明显的代谢变化，从而导致信号级联反应的激活和调控线粒体生物合成的基因的表达。因此，间歇性运动比连续运动能更有效地激活线粒体生物合成。在适应有氧训练的骨骼肌中，通过运动强度激活线粒体生物合成，主要与AMP激活的蛋白激酶/PGC-1α通路，PGC-1α调控的基因的表达，以及来源于由cAMP反应元件结合蛋白1相关转录因子及其共激活因子调控的诱导型可变启动子AP的PPARGC1A的表达有关。     

瘦素与胰岛素抵抗关系及运动

瘦素与胰岛素关系密切,瘦素功能的发挥在胰岛素抵抗的发生发展过程中起着重要作用,其功能的紊乱是发生胰岛素抵抗的重要原因之一。瘦素和胰岛素之间存在相互调节,瘦素还参与胰岛素调节的细胞间信号传导通路的调控,在发挥各自生理功能的细胞间信号通路上两者存在交叉通路。瘦素和运动均可刺激肌肉中蛋白激酶（AMPK）的活化,增加AMPK的含量,提高了胰岛素（Insulin）的敏感性,加强了肌细胞对葡萄糖的摄入。     

运动、转录因子和线粒体的生物合成

转录因子高度依赖共激活分子从转录水平调控运动诱导生理性适应过程.骨骼肌线粒体核染色体的交互作用取决于转录因子(NRF-1,NRF-2、PPARa、ERRa、Sp1等)和PGC-1家族成员(PGC-1a、PGC-1β和PRC)的相关影响.这些分子组成非常复杂的信号网络,广泛参与耐力训练诱导的线粒体的生物合成.但是这些蛋白对生成新的线粒体的确切的贡献很难进行区分.这些转录因子的目标基因大部分涉及到线粒体的生物合成和细胞的新陈代谢,其转录调控方式可能为了解运动性能量变化特征的信号通路与线粒体生物合成及其功能之间的关系提供基本框架.     

MtDNA突变诱导的细胞凋亡通路对Sarcopenia的作用运动对其影响的分子机制

Sarcopenia是一种随年龄的增加，骨骼肌力量和质量降低损失的老年人多发病症。Sarcopenia发生的具体机制尚未完全明晰，目前一些证据证明线粒体机能障碍和失调的细胞凋亡信号通路在其发病和进展的过程中起到关键作用。此外有研究发现运动训练可以通过改善线粒体机能及影响细胞凋亡信号传导，对衰老骨骼肌产生积极影响。     

运动因子在心血管功能中的调控作用及相关机制研究进展

心血管疾病(cardiovascular disease,CVD)是包括动脉粥样硬化、心力衰竭、心脏缺血后再灌注损伤和心肌梗死等血管和心脏的复杂病症。血管内皮细胞、平滑肌细胞和心肌细胞生理功能障碍是诱发CVD的关键因素。研究表明,运动能够对心脏和动脉的形态、功能起到积极的调控作用,可作为CVD非药物疗法的重要手段之一。运动可通过调控多种运动因子的表达水平,如肌肉分泌的Fstl1、Irisin和MSTN,脂肪分泌的Omentin、Apelin、CTRP3和CTRP9,肝脏分泌的FGF21、ANGPTL3和ANGPTL4等,进而调控血管内皮细胞、平滑肌细胞和心肌细胞的分化、增殖和凋亡,从而发挥其防治CVD作用。本文试图梳理肌肉、脂肪和肝脏分泌的运动因子与调控心脏和动脉功能之间的相关信号通路及其机制,为运动干预防治CVD提供新的思路。     

运动与丝裂原活化蛋白激酶信号系统的研究动态

丝裂原活化蛋白激酶信号系统(mitogen activated protein kinase，MAPKs)在细胞的信号传导中起着很重要的作用。其中以ERK1／2、JNK／SAPK、p38研究得最为深入。运动能够激活骨骼肌中MAPKs信号传导系统。不同运动方式、不同类型的肌肉可以影响到MAPKs的激活，而且激活后MAPKs具有不同的时相性。MAPKs对运动后骨骼肌的适应性变化具有重要作用。     

COX-2/PGE-2信号通路在末端病中的作用机制

末端病是运动员中发生的常见病,目前对末端病的组织形态学已经有了深入的研究,而关于其发生机制,特别是分子机制目前仍不清楚。研究证实,末端区主要结构和附属结构组织中发生病变时都会存在大量PGE-2表达,COX-2是PGE-2激活的关键限速酶,因此COX-2/PGE-2信号通路可能与末端病的发生发展有着重要联系。对COX-2/PGE-2信号通路进行深入的研究,将有利于揭示末端病发生的分子机制,也有助于未来靶向治疗末端病。本文就COX-2/PGE-2信号通路分子机制及其与末端病发生的关系作一综述。     

耐力、力量和混合运动对成年C57BL/6小鼠骨骼肌卫星细胞激活信号通路的影响

目的:研究耐力、力量、混合运动3种训练方式激活静息状态卫星细胞的能力.方法:将32只3月龄C57BL/6小鼠随机分成4组:安静组(C,n=8),耐力运动训练组(E,n=8),力量运动训练组(S,n=8),混合运动训练组(M,n=8).经过28周运动干涉后,采用实时荧光定量PCR法检测胫骨前肌卫星细胞激活信号通路中相关基因(nNOS,MMP-2,HGF,c-met) mRNA的转录水平.结果:1)与安静组相比,3组运动训练组C57BL/6小鼠胫骨前肌与体重的比值增加;2)耐力训练组nNOS,HGF,c-met mRNA转录水平显著增加,MMP-2mRNA无显著性差异;3)力量训练组nNOS,MMP-2,HGF,c-met mRNA转录水平显著增加;4)混合训练组nNOS,MMP-2,c-met mRNA转录水平无显著性变化,HGF mRNA转录水平显著增加.结论:力量运动对骨骼肌中卫星细胞的激活具有明显的促进作用,在维持骨骼肌卫星细胞池的数量和促进骨骼肌肥大中具有显著意义;耐力运动能促进卫星细胞的激活,在防止骨骼肌中卫星细胞数量减少,在维持骨骼肌质量和力量上,也有其可取之处;混合训练组在促进卫星细胞激活的过程中,混合运动的效果并不是预期所设想的耐力和力量运动的效果叠加,提示在维持卫星细胞数量和促进骨骼肌肥大上应考虑运动强度、时间和频率,合理安排耐力和力量运动.     

运动和细胞信号分子的交互作用及骨骼肌肥大调控机制

运动能促进身体组织和器官的有利改变,如运动调控骨骼肌的质量和力量变化。一方面,近期研究认为,细胞信号分子对骨骼肌卫星细胞的状态有决定性作用,如激活、增殖、分化、融合等促进骨骼肌重塑过程;另一方面,运动刺激骨骼肌中生长因子合成和分泌的变化,对骨骼肌细胞信号分子的传递与骨骼肌肥大密切相关。目前,国内外鲜有报道从运动和细胞信号分子交互作用探究运动促进骨骼肌肥大的机制。因此,研究试图对运动和多个细胞信号分子的交互作用进行综述,以期为人体复杂系统中骨骼肌肥大机制提供新的研究思路。     

破骨细胞分化、形成过程中表现型特点

综述认为,体外培养破骨细胞是研究骨吸收机理和筛选治疗骨质疏松症药物的基础,建立破骨细胞的分离培养体系,有助于揭示骨吸收机理,了解破骨细胞的生物特性,为破骨细胞学及相关疾病的发病机制研究和防治提供理论依据。因此,了解体外培养的破骨细胞在分化、形成过程中的一些特异性分化抗原或蛋白显得尤其重要。     

运动性心肌肥厚中PKC信号通路研究进展

心肌肥厚是心脏受到刺激后的一种代偿反应。心肌的生理性肥厚可提高心脏机能,但病理性肥厚则会引起心血管疾病心律失常发病和死亡,亦是运动员发生猝死的原因之一。明确运动性心肌肥厚的机制,可为保护运动员心脏提供理论依据。目前为止,形成心肌肥厚的信号通路包括PKC、蛋白激酶B（Akt）、钙调神经磷酸酶（CaM）、丝裂原活化蛋白激酶...     

胰岛素信号通路在运动改善阿尔茨海默病中的作用机制

阿尔茨海默病(AD)是目前最为常见的痴呆类型,其发病机制复杂,尚未完全阐明。研究发现,胰岛素信号通路在AD发病机制中发挥重要作用。运动可以通过激活胰岛素信号通路,调控下游分子表达,改善AD病理表现。从磷脂酰肌醇-3-激酶/丝苏氨酸激酶(PI3K/AKT)、丝裂原活化蛋白酶(MAPK)和Wnt 3条胰岛素信号通路视角切入,探讨运动改善AD的可能分子机制,为AD治疗提供理论依据。     

细胞自噬的分子学机制及运动训练的调控作用

细胞自噬(autophagy)是真核细胞中普遍存在的生命现象,是将细胞内变形、衰老或损伤的蛋白质和细胞器转运到溶酶体腔中消化降解的一种代谢过程。它的分子发生机制和信号调控机制非常复杂且高度保守,其中,mTOR和Beclin1作为各种调控通路的汇集点发挥了至关重要的作用。不同形式与强度的运动训练对细胞自噬也有一定的调节作用。一般来说,适宜强度的运动训练可通过上调细胞自噬水平,降解由于运动刺激所积累的损伤细胞器和代谢废物,为细胞再生提供一定的能量与合成底物,并在抑制自噬相关疾病的发生发展方面具有建设性作用。但过度训练则会因为细胞自噬的过度激活从而过多降解胞浆中的蛋白质和细胞器,导致细胞损伤或疲劳,甚至可能诱发自噬性细胞死亡。另外,运动训练还能通过调节与细胞自噬相关的信号通路对骨骼肌质量产生重要作用。     

Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A–Smad2/3 in rats following myocardial infarction

PurposeThe aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1 (FSTL1), which may induce cardioprotection in rats following myocardial infarction (MI) by inducing angiogenesis.MethodsMale, adult Sprague-Dawley rats were randomly divided into 5 groups (n = 12 in each group): sham group (S), sedentary MI group (MI), MI + resistance exercise group (MR), MI + adeno-associated virus (AAV)–FSTL1 injection group (MA), and MI + AAV–FSTL1 injection + resistance exercise group (MAR). The AAV–FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle. The MI model was established by ligation of the left anterior descending coronary artery. Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder. Heart function was evaluated by hemodynamic measures. Collagen volume fraction of myocardium was observed and analyzed by Masson's staining. Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-β receptor 1 (TGFβR1) inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1. Angiogenesis, cell proliferation, and disco interacting protein 2 homolog A (DIP2A) location were observed by immunofluorescence staining. The expression of FSTL1, DIP2A, and the activation of signaling pathways were detected by Western blotting. Angiogenesis of endothelial cells was observed by tubule experiment. One-way analysis of variance and Student's t test were used for statistical analysis.ResultsResistance exercise stimulated the secretion of skeletal muscle FSTL1, which promoted myocardial angiogenesis, inhibited pathological remodeling, and protected cardiac function in MI rats. Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart. Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A, while TGFβR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A, which was not conducive to angiogenesis. FSTL1 bound to the receptor, DIP2A, to regulate angiogenesis mainly through the Smad2/3 signaling pathway. FSTL1–DIP2A directly activated Smad2/3 and was not affected by TGFβR1.ConclusionDynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1, which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A–Smad2/3 signaling pathway in MI rats.     

The response of intracellular signaling and muscle-protein metabolism to nutrition and exercise

Abstract

In recent years, a body of literature examining the response of muscle-protein metabolism to exercise and nutrition has arisen. Developments in methods, especially stable isotopic tracer methodology, have allowed much information to be gathered in vivo in humans. The metabolic mechanism behind increased muscle mass requires that muscle-protein synthesis exceeds breakdown, i.e., net muscle-protein synthesis. Increased net muscle-protein balance may occur due to exercise, but net synthesis may occur only with the addition of nutrients, particularly a source of amino acids. The major impact of increased amino acid availability on net muscle-protein balance is due to stimulation of muscle-protein synthesis and less to inhibition of muscle-protein breakdown. Amino acids seem to stimulate muscle-protein synthesis, not only by mass action, i.e., providing substrate, but also as signals for initiation of protein synthesis. Stimulation of muscle-protein synthesis by amino acid ingestion may be linked to increased intracellular amino acid levels and/or to changing amino acid levels in the blood. Carbohydrate ingestion, most likely through the action of insulin, also may play a role in the response of muscle to exercise and nutrition. There is very little research in humans in vivo on the intracellular signaling that is linked to muscle-protein synthesis. It is clear that intracellular signaling responds to both insulin and amino acids, but the interactions with exercise are not well known; however, the details of the pathways have only just begun to be investigated, especially in humans. Delineation of these pathways is complicated, and there is little doubt that multiple intracellular signaling pathways with several levels of communication are involved in the hypertrophy process in response to nutrition and exercise. A systematic investigation of the relationship of the signaling to insulin and amino acids combined with exercise will provide important information, especially for populations vulnerable to muscle loss.     

运动性疲劳与骨骼肌细胞凋亡的研究进展

细胞凋亡是由基因控制的细胞死亡过程，它对于多细胞生物的生存和发展以及维护其自身的稳定有极其重要的作用。从细胞凋亡的机制及运动性疲劳与凋亡的关系入手，综述了国内外在这方面的研究进展，以便为寻找新的运动性疲劳的判断和消除手段，提供一些新的思路。     

Dynamic resistance exercise increases skeletal muscle-derived FSTL1 inducing cardiac angiogenesis via DIP2A–Smad2/3 in rats following myocardial infarction

PurposeThe aim of this study was to investigate the potential of dynamic resistance exercise to generate skeletal muscle-derived follistatin like-1 (FSTL1), which may induce cardioprotection in rats following myocardial infarction (MI) by inducing angiogenesis.MethodsMale, adult Sprague-Dawley rats were randomly divided into 5 groups (n = 12 in each group): sham group (S), sedentary MI group (MI), MI + resistance exercise group (MR), MI + adeno-associated virus (AAV)–FSTL1 injection group (MA), and MI + AAV–FSTL1 injection + resistance exercise group (MAR). The AAV–FSTL1 vector was prepared by molecular biology methods and injected into the anterior tibialis muscle. The MI model was established by ligation of the left anterior descending coronary artery. Rats in the MR and MAR groups underwent 4 weeks of dynamic resistance exercise training using a weighted climbing-up ladder. Heart function was evaluated by hemodynamic measures. Collagen volume fraction of myocardium was observed and analyzed by Masson''s staining. Human umbilical vein vessel endothelial cells culture and recombinant human FSTL1 protein or transforming growth factor-β receptor 1 (TGFβR1) inhibitor treatment were used to elucidate the molecular signaling mechanism of FSTL1. Angiogenesis, cell proliferation, and disco interacting protein 2 homolog A (DIP2A) location were observed by immunofluorescence staining. The expression of FSTL1, DIP2A, and the activation of signaling pathways were detected by Western blotting. Angiogenesis of endothelial cells was observed by tubule experiment. One-way analysis of variance and Student''s t test were used for statistical analysis.ResultsResistance exercise stimulated the secretion of skeletal muscle FSTL1, which promoted myocardial angiogenesis, inhibited pathological remodeling, and protected cardiac function in MI rats. Exercise facilitated skeletal muscle FSTL1 to play a role in protecting the heart. Exogenous FSTL1 promoted the human umbilical vein vessel endothelial cells proliferation and up-regulated the expression of DIP2A, while TGFβR1 inhibitor intervention down-regulated the phosphorylation level of Smad2/3 and the expression of vascular endothelial growth factor-A, which was not conducive to angiogenesis. FSTL1 bound to the receptor, DIP2A, to regulate angiogenesis mainly through the Smad2/3 signaling pathway. FSTL1–DIP2A directly activated Smad2/3 and was not affected by TGFβR1.ConclusionDynamic resistance exercise stimulates the expression of skeletal muscle-derived FSTL1, which could supplement the insufficiency of cardiac FSTL1 and promote cardiac rehabilitation through the DIP2A–Smad2/3 signaling pathway in MI rats.