B淋巴细胞瘤-2/腺病毒E1B 19kDa相互作用蛋白3介导的线粒体自噬机制及其调控肌源性挛缩发生的研究进展

线粒体自噬是一种自噬的形式,是目前已知的选择性清除线粒体的途径。近年来,B淋巴细胞瘤-2/腺病毒E1B 19kDa相互作用蛋白3（BNIP3）因其在线粒体自噬中的潜在作用而备受关注。尽管对BNIP3在线粒体自噬中的调控机制认识不断增加,但在肌源性挛缩的发生过程中,BNIP3介导的线粒体自噬的作用及其机制仍知之甚少。在肌源性挛缩发生过程中,典型的病理特征表现为骨骼肌萎缩和纤维化。因此,本文对BNIP3及其在线粒体自噬中的调控机制进行了系统回顾,并对BNIP3介导的线粒体自噬影响骨骼肌萎缩和纤维化的研究进行了综述,以期为肌源性挛缩的治疗提供新的思路。     

运动诱导细胞自噬在老年肌少症康复中的研究进展

老年肌少症是一种与衰老相关的疾病,由于蛋白质合成和降解两者之间的不平衡,导致骨骼肌肉的质量和强度的降低。细胞自噬作为调节体内蛋白质代谢平衡的保守机制,能够被运动诱导的腺苷酸活化蛋白激酶(AMPK)、胰岛素样生长因子(IGF)/蛋白激酶B (Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)及磷脂酰肌醇3激酶(PI3K)/Akt/mTOR等多条信号通路途径调节。而运动激活的细胞自噬调控不同生理病理条件下骨骼肌重塑与内环境稳态的稳定,是骨骼肌健康维持的关键。本文总结不同运动诱导的细胞自噬在老年肌少症的预防、治疗和康复中的作用与潜在的分子机制。     

肌少症与营养

肌少症是以进行性、广泛性的骨骼肌质量减少、肌力下降和功能减退为特征的综合征,其发病率较高,可降低老年人的生命质量,增加病残率和死亡率,严重威胁老年人群的身体健康。肌少症受多种影响因素的作用,近年来研究发现肌少症与营养关系密切,且干预性研究结果显示营养剂的补充可有效改善骨骼肌肌力和功能,增加骨骼肌质量。因此,补充营养有望成为防治肌少症的重要方法之一。本文就肌少症与营养如蛋白质、维生素D、n-3多不饱和脂肪酸的关系进行综述,以期加强临床医师对肌少症的认识,为我国肌少症的干预性研究提供依据。     

线粒体自噬参与帕金森病发病机制的研究进展

帕金森病是中老年人常见的中枢神经系统退行性疾病,近年的研究表明线粒体自噬是帕金森病的发病机制之一。目前已知帕金森病相关基因PINK1、PARKIN、SNCA、DJ-1、LRRK2以及ATP13A2和GBA均参与线粒体自噬的调节。其中PINK1参与线粒体代谢、线粒体动力和异常蛋白的降解过程,并参与PARKIN移位至受损线粒体触发线粒体自噬;PARKIN参与泛素-蛋白降解途径,调节自噬小体吞噬、降解陈旧线粒体,以保护线粒体DNA、维持线粒体呼吸链活性来发挥细胞保护作用;DJ-1参与细胞应激环境下线粒体活性和形态的调节;SNCA编码的α-突触核蛋白通过影响自噬小体的形成、调节线粒体动力和保持线粒体的钙平衡来调控线粒体自噬;LRRK2基因突变也可以引发线粒体自噬。此外,环境因素也可能直接或间接地对线粒体自噬产生调控。本文将对线粒体自噬与帕金森病之间的关联作一简要综述。     

针刺对大负荷运动大鼠骨骼肌线粒体结构和功能的影响

目的:研究针刺对大负荷运动大鼠骨骼肌线粒体结构与功能的影响,探讨针刺干预对运动性骨骼肌损伤的恢复和预防的作用。方法:128只成年雄性SD大鼠,随机分为4组:空白对照组(C组,n=8)、单纯运动组(E组,n=40)、单纯针刺组(A组,n=40)和运动针刺组(EA组,n=40)。其中,E和EA组进行一次下坡跑运动,A组和EA组在运动后即刻施加针刺处理。各组根据干预后不同时相又分为0h、12h、24h、48h和72h组(n=8),分别于对应时间点分离比目鱼肌进行检测。使用透射电子显微镜观察骨骼肌线粒体超微结构变化,采用ELISA方法检测各组大鼠比目鱼肌线粒体定量酶CS的含量以及线粒体呼吸链复合体Ⅱ、Ⅳ的活性,应用Western Blot方法检测骨骼肌COXⅠ的蛋白表达。结果:单纯针刺后骨骼肌COXⅠ蛋白表达上调。大负荷运动后比目鱼肌线粒体出现明显肿胀、肌膜下积聚等超微结构异常变化,且伴有大量自噬体形成,同时柠檬酸合成酶(CS)的含量明显减少,呼吸链复合体Ⅱ、Ⅳ活性以及COXⅠ蛋白表达出现一过性的下调(P0.05)。与运动组相比,运动针刺后明显改善了大负荷运动所致线粒体超微结构的异常变化,有自噬溶酶体的出现,CS含量有所增加,呼吸链复合体Ⅱ活性及COXⅠ蛋白表达上调。结论:针刺促进了大负荷运动后骨骼肌线粒体结构的恢复,有效增加了运动后线粒体的数量,减轻了大负荷运动对线粒体功能的损害。     

肌少症的运动康复机制研究进展

肌少症是由于衰老导致的骨骼肌力量下降、功能减退的增龄性肌肉减少综合征。目前,运动作为一种非药物治疗肌少症的康复手段,可有效改善骨骼肌质量并延缓其进展。本文就肌少症病理机制、不同运动方式对肌少症的防治与康复作用和潜在机制进行系统综述,以期为肌少症的运动康复提供参考与理论依据。     

骨骼肌钝挫伤的损伤与修复机制研究进展CSCD

总结骨骼肌钝挫伤的损伤与修复机制,并从肌卫星细胞增殖和分化学说、Ca^(2+)介导的细胞膜修复学说、内质网应激学说以及自噬学说等方面进行阐述。肌再生依赖于周围卫星细胞的分化、增殖来促进骨骼肌再生,从而修复受损肌肉的功能。调控肌卫星细胞成肌分化的相关信号通路主要包括RBP-Jκ/Notch信号、Wnt信号和P13K/Akt/mTOR信号通路。其中Notch信号通路通过调控肌卫星细胞自我更新和分化来维持肌干细胞的稳态。P13K/Akt/mTOR信号通路对肌卫星细胞的成肌分化具有正向调控作用,能够促进骨骼肌再生。然而,当前的研究对Wnt信号通路在成熟骨骼肌再生过程中的作用存在争议,激活Wnt信号通路是否有利于骨骼肌损伤与修复需要更多的研究来进行论证。Ca^(2+)介导细胞膜修复对骨骼肌钝挫伤后肌膜修复、细胞存活至关重要。但是骨骼肌损伤后引起钙泵结构受损或功能下降使Ca^(2+)回收受阻,Ca^(2+)失调通过促进线粒体的活性氧(ROS)的产生和扰乱内质网腔内的蛋白质折叠,有助于异常的蛋白质生成,内质网中异常折叠蛋白生成增多,超过其阈值并发生聚集、滞留,最终诱导内质网过度应激。内质网过度应激可通过PKC或FAM134B途径介导细胞自噬,自噬通过自我降解异常细胞器或错误折叠蛋白,以更新并维持细胞内环境稳态。关于自噬在骨骼肌损伤修复中的作用机制,除了内质网过度应激诱导,有关报道认为钝挫伤诱发的局部组织供氧不足,促使大量的ROS产生或AMPK信号通路的激活,均可诱导线粒体自噬而维持线粒体的稳定,减少能量消耗,从而有利于促进钝挫伤修复。虽然骨骼肌钝挫伤的损伤修复的机制错综复杂,但上述学说之间有交叉之处,因此对于骨骼肌钝挫伤的损伤修复机制研究可以围绕以上学说进一步深入研究,以明确不同学说在骨骼肌损伤修复的不同阶段如何发挥协同作用。     

心脏缺血再灌注损伤与线粒体质量控制

心脏缺血再灌注(ischemia-reperfusion, I/R)损伤是心脏疾病中常见并发症，其发生机制复杂且尚未完全阐明。线粒体质量控制(mitochondrial quality control, MQC)是维持心肌细胞正常功能和适应能力的关键过程。MQC系统参与调节线粒体生物合成、线粒体动力学以及自噬环节，保护心肌细胞免受I/R损伤的影响。目前，MQC成为心脏I/R损伤的新型靶向治疗策略。本文通过概述MQC与心脏I/R损伤之间的联系及近期研究机制进展，旨在提供新的思路和研究方向，为心脏疾病的治疗和预防提供理论依据。     

糖尿病肌少症影像学研究进展

肌少症是一种以骨骼肌质量减少及功能减退为特征的老年综合征,也是糖尿病的慢性并发症之一,可导致一系列不良的健康后果。早期识别诊断糖尿病肌少症对于防止疾病进展、保证患者生活质量具有重大意义,而影像技术对于评估肌少症早期骨骼肌质量改变方面具有极大的临床价值。作者主要阐述不同影像技术对于糖尿病肌少症的评估价值及特点。     

线粒体及其自噬在精子发生过程中的作用研究

精子活力是衡量精液质量和男性生育能力的一个重要临床指标。精子运动所需能量来自线粒体呼吸链的氧化磷酸化,线粒体形态、数目、酶活性、DNA完整性及活性氧（ROS）产生等的改变都影响精子生理功能。线粒体自噬是一种选择性的细胞自噬途径,作为一种清除损伤的线粒体和过量产生的ROS的防御机制,确保细胞内线粒体功能稳定,促进应激环境中细胞的存活。因此,推测精子细胞可能通过线粒体自噬这一特异性的选择途径清除异常线粒体以保护精子细胞生存并维持精子活力,自噬参与了精子的发生过程。     

Association between skeletal muscle mass index and lung function/respiratory muscle strength in older adults requiring long-term care or support

[Purpose] We focused on skeletal muscle mass index, one of the biomarkers of sarcopenia, and investigated the association between skeletal muscle mass index and the parameters of lung function and respiratory muscle strength. [Participants and Methods] After applying the exclusion criteria, we included, in this cross-sectional study, 120 community-dwelling older adults aged ≥65 years who required long-term care/support and underwent ambulatory rehabilitation under the long-term care insurance system in Japan. We measured the skeletal muscle mass index, forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate, maximum expiratory pressure, and maximum inspiratory pressure. The data were analyzed using Pearson correlation coefficient and multiple regression analysis. [Results] The skeletal muscle mass index was positively correlated with only maximum expiratory pressure for both male and female participants by Pearson’s correlation coefficient. With the skeletal muscle mass index as a dependent variable, only the maximum expiratory pressure was significant for both male and female participants by the multiple regression analysis. [Conclusion] Therefore, the findings of this study suggested that compared with lung function tests, maximum expiratory pressure, which is an indicator of respiratory muscle strength, is related to muscle mass. Maximum expiratory pressure might be the most useful indicator for sarcopenia.Key words: Maximum expiratory pressure, Sarcopenia, Skeletal muscle mass index     

肌少症训练综合干预应用于老年轻型急性缺血性脑卒中患者的效果观察

目的探讨肌少症训练综合干预应用于老年轻型急性缺血性脑卒中患者的效果。方法将鹤壁市人民医院2018年7月至2020年12月123例老年轻型急性缺血性脑卒中患者按照计算机分组法分为对照组61例,给予常规康复训练干预,观察组62例在对照组基础上给予肌少症训练综合干预,对比两组骨骼肌厚度和指数、认知功能以及肌少症发生情况。结果干预后,观察组肱二头肌、胫前屈肌厚度以及骨骼肌质量指数(ASMI)水平均高于对照组(P<0.05);观察组蒙特利尔认知量表(MoCA)和简易智力状态量表(MMSE)分值均高于对照组(P<0.001);观察组肌少症发生率(4.84%)低于对照组(18.03%),P<0.05。结论肌少症训练综合干预应用于老年轻型急性缺血性脑卒中患者可调节骨骼肌厚度和ASMI,改善认知功能且能减少肌少症发生。     

Muscle wasting associated co-morbidities,rather than sarcopenia are risk factors for hospital mortality in critical illness

BackgroundLow skeletal muscle mass on intensive care unit admission is related to increased mortality. It is however unknown whether this association is influenced by co-morbidities that are associated with skeletal muscle loss. The aim of this study was to investigate whether sarcopenia is an independent risk factor for hospital mortality in critical illness in the presence of co-morbidities associated with muscle wasting.MethodsData of 155 patients with abdominal sepsis were retrospectively analyzed. Skeletal muscle area was assessed using CT-scans at the level of vertebra L3. Demographic and clinical data were retrieved from electronic patient files. Sarcopenia was defined as a muscle area index below the 5th percentile of the general population. Uni- and multivariable analyses were performed to assess the association between sarcopenia and hospital mortality, correcting for age and comorbidities.ResultsThe prevalence of sarcopenia was higher in patients that did not survive until hospital discharge. However, it appeared that this relation was confounded by the presence of chronic renal insufficiency and cancer. These were independent risk factors for hospital mortality, whereas sarcopenia was not.ConclusionIn critically ill patients with abdominal sepsis, muscle wasting associated co-morbidities rather than sarcopenia were risk factors for hospital mortality.     

老年肌少症的评估及干预

肌少症是与增龄相关的骨骼肌减少过程,与活动减少相关,在老年人中常见,可导致跌倒、失能及增加死亡风险。肌少症虽然一直被定义为增龄性的肌量减少和肌力下降,但目前还没有公认的定义,不同的国际工作小组对这种综合征的正确名称(与老年人肌肉和力量的损失相关)仍在争论。随着我国人口老龄化,充分认识肌肉衰减综合征并开展积极防治,对改善老年人生活质量、降低并发症具有重要意义。本文就老年肌少症的肌量、肌强度和日常活动功能评估方法和针对老年肌少症的各种干预方法作一述评。     

Parvalbumin gene transfer impairs skeletal muscle contractility in old mice

Abstract Sarcopenia is the progressive age-related loss of skeletal muscle mass associated with functional impairments that reduce mobility and quality of life. Overt muscle wasting with sarcopenia is usually preceded by a slowing of the rate of relaxation and a reduction in maximum force production. Parvalbumin (PV) is a cytosolic Ca(2+) buffer thought to facilitate relaxation in muscle. We tested the hypothesis that restoration of PV levels in muscles of old mice would increase the magnitude and hasten relaxation of submaximal and maximal force responses. The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old (26 month) C57BL/6 mice received electroporation-assisted gene transfer of plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA muscles were assessed in situ 14 days after transfer. In old mice, muscles with increased PV expression had a 40% slower rate of tetanic force development (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than control values, respectively (p<0.05). Muscles with increased PV expression from old mice had an 18% lower maximum specific (normalized) force than controls, and absolute force was ～26% lower at higher stimulation frequencies (150-300?Hz, p<0.05). In contrast, there was no effect of increased PV expression on TA muscle contractile properties in young and adult mice. The impairments in skeletal muscle function in old mice argue against PV overexpression as a therapeutic strategy for ameliorating aspects of contractile dysfunction with sarcopenia and help clarify directions for therapeutic interventions for age-related changes in skeletal muscle structure and function.     

Mitochondria as sources and targets of damage in cellular aging

Mitochondria are considered as the most important cellular sources and targets of free radicals. They are also a source of signalling molecules that regulate cell cycle, proliferation, and apoptosis. Denham Harman postulated the free radical theory of aging in 1956. Previously Rebecca Gershman showed that radiation toxicity could be attributed to free radical damage. Subsequently, Jaime Miquel formulated the mitochondrial free radical theory of aging. We have shown that mitochondrial size, membrane potential, inner membrane mass and peroxide production is altered inside cells in old animals. These result in an increase in the oxidative damage to mitochondrial DNA with aging that can be prevented by antioxidant supplementation. Aging is also associated with a lower renewal of mitochondria. This is mainly due to the lack of reactivity of proliferator-activated receptor-γ (PPAR-γ) coactivator 1α (PGC-1α) in old animals. PGC-1α acts as a master regulator of energy metabolism and mitochondrial biogenesis and recent evidence shows that it interacts with p53 and telomerase. The promotion of mitochondriogenesis is critical to prevent aging. In skeletal muscle it has relevance to prevent sarcopenia and frailty.     

11种运动对老年肌少症患者身体功能改善效果的网状Meta分析

目的 通过网状Meta分析评价11种运动训练对老年肌少症患者身体功能、肌肉力量和肌肉质量改善效果的影响。 方法 检索Web of Science、PubMed、Embase、Cochrane Library、CINAHL、中国知网、中国生物医学文献数据库、万方数据库和维普数据库中关于运动训练对老年肌少症患者身体功能、肌肉力量和肌肉质量改善效果的随机对照试验。检索时限为建库至2022年1月。采用Stata 15.0软件进行网状Meta分析。 结果 纳入34项研究,共2 199例患者。网状Meta分析结果表明,与非运动对照组相比,阻力训练、小组综合训练、八段锦、全身振动训练、家庭综合训练可改善老年肌少症患者的身体功能（P<0.05）;阻力训练和壶铃训练可改善老年肌少症患者的握力（P<0.05）;阻力训练可改善老年肌少症患者的骨骼肌指数（P<0.05）。 结论 在改善老年肌少症患者身体功能、肌肉力量和质量方面,阻力训练是目前最优的运动干预措施,其次为小组综合训练和全身振动训练,但仍需更多研究进一步论证。     

上臂围和小腿围在社区老年肌少症患者筛查诊断中的应用

目的 探讨上臂围和小腿围与肌肉量的相关关系及其对肌量减少和肌少症的筛查诊断效果和最佳诊断截断值。方法 2020年3月至8月,方便抽取831例社区老年人(≥ 60岁)作为研究对象,采用身体成分测试仪检测肌肉量等指标,同时进行上臂围和小腿围的测量,握力及步速测试。上臂围、小腿围与肌肉量等指标的相关性行Pearson相关分析,受试者操作特征(ROC)曲线分析上臂围和小腿围对肌量减少和肌少症的诊断效果,并利用约登指数(YI)确定最佳诊断截断值。结果 上臂围和小腿围与四肢骨骼肌含量(ASM)和骨骼肌质量指数(SMI)呈显著正相关(r = 0.6~0.8, P < 0.001)。上臂围诊断肌量减少的ROC曲线下面积(AUC)是男性0.888、女性0.787,小腿围是男性0.933、女性0.854;上臂围最佳截断值男性和女性均为26 cm,小腿围男性34 cm、女性33 cm。上臂围诊断肌少症的AUC是男性0.902、女性0.744,小腿围是男性0.923、女性0.832;其最佳截断值无性别差异,分别是26 cm和33 cm。在社区老年男性和女性中,年龄、上臂围、小腿围、握力和步速等多指标对肌量减少和肌少症联合诊断的AUC均大于0.85。结论 社区老年人中,上臂围和小腿围均与肌肉量呈正相关,且对肌量减少和肌少症具有较好的诊断效果;多指标的联合诊断可显著提高上臂围在女性中的诊断效果。     

Mitochondrial dysfunction in patients with primary congenital insulin resistance

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic lipid species in muscle and elsewhere, impairing insulin action on glucose metabolism. Alternatively, however, defects in insulin signaling may be primary events that result in mitochondrial dysfunction, or there may be a bidirectional relationship between these phenomena. To investigate this, we examined mitochondrial function in patients with genetic defects in insulin receptor (INSR) signaling. We found that phosphocreatine recovery after exercise, a measure of skeletal muscle mitochondrial function in vivo, was significantly slowed in patients with INSR mutations compared with that in healthy age-, fitness-, and BMI-matched controls. These findings suggest that defective insulin signaling may promote mitochondrial dysfunction. Furthermore, consistent with previous studies of mouse models of mitochondrial dysfunction, basal and sleeping metabolic rates were both significantly increased in genetically insulin-resistant patients, perhaps because mitochondrial dysfunction necessitates increased nutrient oxidation in order to maintain cellular energy levels.