Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK‑PGC‑1α signaling pathway and alters the muscle fiber composition of sheep

Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.

Mitochondrial dysfunction in type 2 diabetes:A neglected path to skeletal muscle atrophy

Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.

Significance of bilayer-forming phospholipids for skeletal muscle insulin sensitivity and mitochondrial function

Phosphatidylcholine(PC) and phosphatidylethanolamine(PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca^(2+) ATPase(SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.

L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death

AIM To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells.METHODS Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine(a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death. RESULTS Associated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species(ROS), especially under pathological conditions. High levels of ROS are known to induce injuries in cell structure as they interact at many levels in cell function. In C2C12 cells, a treatment with menadione induced a loss of transmembrane mitochondrial potential, an increase in mitochondrial production of ROS; it also induces autophagy and was able to provoke cell death. Pre-treatment of the cells with L-carnitine reduced ROS production, diminished autophagy and protected C2C12 cells against menadione-induced deleterious effects. CONCLUSION In conclusion, L-carnitine limits the oxidative stress in these cells and prevents cell death.

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

Mitochondrial Ca^(2+) uptake in skeletal muscle health and disease

Muscle uses Ca2＋ as a messenger to control contraction and relies on ATP to maintain the intracellular Ca2＋ homeostasis. Mi- tochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca2＋ from their surroundings, a process called mitochondrial Ca2＋ uptake. Under physiological conditions, Ca2＋ uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca2＋ overload, which activates down- stream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca2＋ uptake could shape spatio-temporal pat- terns of intracellular Ca〉 signaling. Malfunction of mitochondrial Ca2＋ uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca2＋ levels. Besides the sudden elevation of Ca2＋ level induced by action potentials, Ca2＋ transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca2＋ uptake is fast and big enough to shape intracellular Ca2＋ signaling during excitation-contraction coupling and creates technical challeng- es for quantification of the dynamic changes of Ca2＋ inside mitochondria. This review focuses on characterization of mito- chondrial Ca2＋ uptake in skeletal muscle and its role in muscle physiology and diseases.

Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles

Objective:To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo.Methods:Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine(BrdU)assay kit.Western blot analysis was performed to determine the protein expressions of related factors.The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay.Chemical composition analysis was performed using high-performance liquid chromatography(HPLC).Results:Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway.It also induced metabolic changes,increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase.In an in vivo study,the extract-treated mice showed improved motor abilities,such as muscular endurance and grip strength.Additionally,HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength.Conclusions:Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles,suggesting its potential as an effective natural agent for improving muscular strength.

Exercise is mitochondrial medicine for muscle

Mitochondria are vital organelles that provide energy for muscle function.When these organelles become dysfunctional,they produce less energy as well as excessive levels of reactive oxygen species which can trigger muscle atrophy,weakness and loss of endurance.In this review,molecular evidence is provided to show that exercise serves as a useful therapeutic countermeasure to overcome mitochondrial dysfunction,even when key regulators of organelle biogenesis are absent.These findings illustrate the complexity and compensatory nature of exercise-induced molecular signaling to transcription,as well as to post-transcriptional events within the mitochondrial synthesis and degradation(i.e.turnover)pathways.Beginning with the first bout of contractile activity,exercise exerts a medicinal effect to improve mitochondrial health and whole muscle function.

Age-dependent peculiarities modulation of activity of aldehyde scavenger enzymes in mitochondria of rat thigh muscle during stress

The purpose of this study was a comparative investigation of activity of aldehyde scavenger enzymes in mitochondrial fraction of a thigh muscle in intact and immobilized rats of different ages. It has been shown that 12- month-old （adult） rats have high basal levels of aldehyde dehydrogenase, aldehyde reductase and glutathione transferase activity in mitochondrial fraction of thigh muscle. Aldehyde dehydrogenase activity increases during immobilization stress in adult rats. This change promote to enhance the effectiveness of utilization of carbonyl products of free radical oxidation in mitochondria of skeletal muscle of 12-month-old rats during stress. Immobilization of old and pubertal rats is accompanied by metabolic preconditions leading to accumulation of endogenous aldehydes in mitochondria, and, as a result, to the injury of muscular fibers and intensification of sarcopenia manifestations.

Role of PGC-1αin muscle function and aging

This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.

Metabolism and regulation of FNDC 5 in skeletal muscle

Purpose： Fibronectin type III domain-containing protein 5 （FNDC5）, also known as irisin, is a myokine secreted from muscle in response to exercise and improves obesity and glucose homeostasis. However, the molecular mecha- nisms that regulate FNDC5 expression and the functional significance of FNDC5 in skeletal muscle remain un- known. In this study, we explored the possible pathways that induce FNDC5 expression and delineated its metabol- ic effects on skeletal muscle. Methods： C2C12 myotubes were treated with various concentrations of Sp-cAMP, forskolin, and ionomycin respectively for various durations. FNDC5 and related metabolic genes＇ expressions were measured by quantitative real-time polymerase chain reaction （qRT-PCR）. Cyclic AMP responsive element-binding protein （CREB） phosphorylation was measured by Western blot. Oxidative phosphorylation was quantified by oxy- gen consumption rate （OCR） measurement using XF-96 analyzer （Seahorse Bioscience）. The statistical signifi- cance was calculated by one-way analysis of variance （ANOVA）. Data were considered significant when P 〈 0.05. Results： We found that cAMP and forskolin dose and time dependently increased FNDC5 expression in C2C12 myotubes. A synergistic effect of forskolin and ionomycin on FNDC5 expression was also found. CREB phosphoryl- ation was elevated in myotubes simultaneously upon these treatments. C2C12 myotubes over expressing CREB dis- plays increased FNDC5 expression as well, suggesting CREB was a regulator of FNDC5 expression. Functionally, irisin treatment enhanced mitochondrial biogenesis of C2C12 myotubes through increasing peroxisome proliferator- activated receptor gamma coactivator-1α （PGC-1α）, nuclear respiratory factor 1 （NRF1） and mitochondrial tran-scription factor A （TFAM） expressions, leading to increase myotube mitochondrial respirations and ATP produc- tion. Conclusions Our observation indicates that irisin is a metabolic modulator of skeletal muscle, whose expres- sion is controlled by cAMP pathway and intracellular level of calcium.

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

Objective： Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes （MELAS） is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. M ELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well. Data Sources： The data used in this review came fi-om published peer review articles from October 1984 to October 2014, which were obtained fiom PubMed. The search term is ＂MELAS＂, Study Selection： lnfornmtion selected from those reported studies is mainly based on the progress on clinical tkatures, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS. Results： MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging （MRI） can provide directional information on this disease. Muscle biopsy has meaningflil value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the lnutation in.3243A〉G of the mitochondrial transfer RNA （Leu （UU R）） gene （MT-TLI）. Conclusions： MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MR1, muscle biopsy, and genetics.

The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes model via mitochondrial protection

This study aimed to evaluate the therapeutic effect of IR-61,a novel mitochondrial heptamethine cyanine dye with antioxidant effects,on diabetes mellitus-induced erectile dysfunction(DMED).Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin(STZ)to induce type 1 diabetes.Eight weeks after STZ injection,all rats were divided into three groups:the control group,DM group,and DM+IR-61 group.In the DM+IR-61 group,the rats were administered IR-61(1.6 mg kg-1)twice a week by intravenous injection.At week 13,erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure,and the penises were then harvested for fluorescent imaging,transmission electron microscopy,histological examinations,and Western blot analysis.Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection.IR-61 treatment significantly improved the maximal ICP of diabetic rats.Additionally,IR-61 ameliorated diabetes-induced inflammation,apoptosis,and phenotypic transition of corpus cavernosum smooth muscle cells(CCSMCs)in penile tissue.IR-61 also attenuated mitochondrial damage,reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuinl(SIRT1),sirtuin3(SIRT3),nuclear factor(erythroid-derived 2)-like 2(Nrf2),and heme oxygenase expression in penile tissue.In conclusion,IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs,which may be mediated by activation of the SIRT1,SIRT3,and Nrf2 pathways.

羊肚菌硒化多糖结构表征及抗运动疲劳作用

目的:研究羊肚菌硒多糖的结构特征及其对运动疲劳大鼠的改善作用。方法:采用超声波辅助热水提取羊肚菌子实体多糖,经DEAE纤维素柱层析和葡聚糖凝胶G-100柱层析洗脱得到纯化多糖(Msp-1),采用硝酸-亚硒酸钠法处理纯化多糖得到羊肚菌硒化多糖(Se-Msp1),分别对Msp-1和Se-Msp1结构表征;通过力竭游泳试验测定大鼠的游泳时间,同时建立大鼠负重游泳模型,设置安静对照组、运动疲劳对照组、阳性对照组(红景天苷,100 mg/kg)、普通多糖组(Msp-1,100 mg/kg)、硒多糖低、中、高剂量组(Se-Msp1,剂量依次为50、100和200 mg/kg),灌胃体积0.1 mL/(10 g·bw),连续灌胃5周,检测大鼠体内血乳酸(blood lactic acid,BLA)、血尿素氮(blood urea nitrogen,BUN)、肝糖原(hepatic glycogen,HG)、肌糖原(muscle glycogen,MG)含量和骨骼肌线粒体中丙二醛(MDA)含量以及超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性,评价Se-Msp1的抗运动疲劳作用。结果:羊肚菌多糖经分离纯化得到的最大组分为Msp-1,占比达到85.25%,红外光谱显示Se-Msp1的异头碳为α构型,且存在Se的特征吸收峰,表明Se-Msp1硒化成功,测得Se-Msp1硒含量为9.56 mg/g,多糖含量为56.34%,糖醛酸含量为36.82%,重均分子量3.482×10^(5) Da,粒径为384.71 nm,电位为-45.78 mV,说明Se-Msp1中硒含量较高且稳定性好,其由甘露糖、葡萄糖醛酸、半乳糖、半乳糖醛酸、半乳糖组成,摩尔比为1:0.42:3.57:3.34:1.86。抗疲劳结果显示,与空白对照组相比,Msp-1和Se-Msp1均极显著提高了大鼠力竭游泳时间(P<0.01),表现出较好的抗疲劳效果;运动疲劳模型结果显示,与运动疲劳对照组相比,Se-Msp1低、中、高剂量组大鼠HG和MG含量均极显著提高(P<0.01),BLA、BUN含量则极显著降低(P<0.01),骨骼肌线粒体中MDA含量同样极显著降低(P<0.01),抗氧化酶活性(SOD、CAT、GSH-Px)则极显著升高(P<0.01),且相比Msp-1,Se-Msp1具有更高的抗氧化活性。结论:制得的羊肚菌硒化多糖(Se-Msp1)结构稳定且具有较高的抗氧化和抗运动疲劳活性,为羊肚菌富硒多糖产品开发提供理论依据。

银质针导热治疗肌筋膜疼痛综合征大鼠骨骼肌线粒体和SIRT3表达的变化

背景:临床研究发现银质针导热治疗对肌筋膜疼痛综合征患者具有良好镇痛作用,但其具体机制仍不清楚。目的:观察银质针导热治疗对肌筋膜疼痛综合征大鼠线粒体超微结构和沉默信息调节因子同源蛋白3变化的影响。方法:26只大鼠随机取20只予以打击结合运动疲劳的方法复制肌筋膜疼痛综合征大鼠模型,造模成功的16只大鼠随机分为模型组和银质针导热组,每组各8只;银质针导热组给予银质针导热处理;剩余6只为正常对照。分别于造模前1 d、造模完成后第1天、银质针导热处理后第14天检测大鼠机械刺激缩足阈值、热缩足潜伏期;银质针导热处理后第14天检测大鼠股内侧肌肌电图电活动,取大鼠右侧股内侧肌分别进行苏木精-伊红染色观察局部形态、透射电镜观察线粒体超微结构、Western blot检测沉默信息调节因子同源蛋白3表达。结果与结论:①痛阈值:与正常组和造模前相比,模型组、银质针导热组造模后机械刺激缩足阈值和热缩足潜伏期显著缩短(P<0.01);经银质针导热处理后,与模型组相比,银质针导热组机械刺激缩足阈值和热缩足潜伏期显著延长(P<0.01);②肌电图:模型组大鼠右侧股内侧出现自发电活动,银质针导热组自发电活动较模型组减少,时限较模型组延长(P<0.01),波幅较模型组降低(P<0.05);③苏木精-伊红染色:正常组大鼠肌纤维排列紧密规则,模型组大鼠肌纤维萎缩、变性,排列紊乱,银质针导热组大鼠肌肉结构紊乱改善;④骨骼肌线粒体微观结构:透射电镜显示正常组肌组织线粒体结构正常;模型组肌组织线粒体肿胀,嵴断裂或消失;银质针导热组肌组织线粒体肿胀明显缓解或趋于正常;⑤沉默信息调节因子同源蛋白3表达:模型组较正常组明显下调,银质针导热组较模型组明显上调(P<0.05);⑥结果表明:肌筋膜疼痛综合征大鼠局部肌肉线粒体出现异常,沉默信息调节因子同源蛋白3的表达下调,提示存在能量代谢障碍;银质针导热处理后线粒体变化恢复,接近正常,且沉默信息调节因子同源蛋白3的表达上调接近正常组,推测银质针导热疗法可能通过促进线粒体修复而改善能量代谢障碍发挥治疗作用。

3-硝基-N-甲基水杨酰胺对肢体缺血再灌注损伤大鼠骨骼肌的保护作用及机制

背景:线粒体活性氧爆发已被证明在骨骼肌缺血再灌注中起着关键作用。3-硝基-N-甲基水杨酰胺(3-nitro-N-methyl salicylamide,3-NNMS)可以有效降低电子传递速度,对肢体缺血再灌注损伤具有潜在的保护作用,但目前尚无明确的研究和临床应用。目的:探讨3-NNMS对肢体缺血再灌注损伤大鼠骨骼肌的保护作用及机制。方法:40只健康8周龄SD大鼠随机分为对照组及3-NNMS的0μg/mL组、25μg/mL组、125μg/mL组,每组10只。除对照组外,其余各组制备肢体缺血再灌注损伤大鼠模型,于再灌注前30 min,向损伤部位注射相应浓度的3-NNMS。再灌注2 h后,心尖取血,取大鼠右下肢股直肌组织进行检测。苏木精-伊红染色观察大鼠股直肌组织病理形态;ELISA检测血清骨骼肌损伤因子肌酸激酶(Creatine Kinase found in the skeletal muscle,CK-MM)、乳酸脱氢酶、髓过氧化物酶水平,并检测股直肌核因子κB、肿瘤坏死因子α、白细胞介素1β、环氧合酶2、丙二醛、活性氧、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶水平,以及股直肌ATP水平、ATPase活性、线粒体呼吸控制率(RCR)水平。结果与结论:①与对照组相比,缺血再灌注模型大鼠血清CK-MM、乳酸脱氢酶、髓过氧化物酶水平升高,股直肌核因子κB、肿瘤坏死因子α、白细胞介素1β、环氧合酶2、丙二醛及活性氧水平升高,过氧化氢酶、谷胱甘肽过氧化物酶水平下降,ATPase活性、线粒体呼吸控制率水平降低;细胞形态不规则,炎性细胞浸润明显,细胞出现肿胀。②与0μg/mL组相比,25μg/mL组大鼠血清CK-MM、乳酸脱氢酶水平降低,股直肌核因子κB、环氧合酶2水平降低,活性氧减少,超氧化物歧化酶活性升高;细胞形态较规则,炎性细胞浸润较轻,细胞肿胀现象缓解。③与0μg/mL组相比,125μg/mL组大鼠血清CK-MM、乳酸脱氢酶、髓过氧化物酶水平降低,股直肌核因子κB、肿瘤坏死因子α、环氧合酶2量减少,丙二醛、活性氧水平降低,超氧化物歧化酶、谷胱甘肽过氧化物酶活性升高,线粒体呼吸控制率水平升高;细胞排列较整齐,轮廓较清晰完整,炎性细胞浸润较轻。④结果说明:3-NNMS可以减轻肢体缺血再灌注引起的骨骼肌功能损伤,其作用机制可能是通过改善线粒体功能、减少活性氧产生、降低氧化应激和炎症反应,进而减轻组织损伤,修复骨骼肌功能。

血管平滑肌细胞线粒体与腹主动脉瘤发生发展的研究进展

腹主动脉瘤(AAA)是以腹主动脉壁发生持续性扩张为主要特点的血管疾病,破裂后常导致严重后果。血管平滑肌细胞(VSMCs)是构成血管中膜的重要组成部分,负责调节血管的直径和血流,以维持正常的血液循环和血压。VSMCs线粒体作为VSMCs氧化代谢的中心,在能量产生和细胞代谢中发挥重要作用。近年来,越来越多的研究表明,VSMCs线粒体功能障碍与AAA的发生发展密切相关。现从VSMCs线粒体与氧化应激和炎症、线粒体DNA损伤、线粒体动力学异常和细胞代谢四个方面探讨VSMCs线粒体损伤在AAA发生发展中的研究进展,旨在为AAA未来的治疗和预防提供新的策略。

黄芩苷调节线粒体动力学平衡后减缓小鼠骨骼肌缺血再灌注损伤的研究

目的研究黄芩苷对小鼠骨骼肌缺血再灌注损伤是否具有抑制作用,该抑制作用是否通过调节线粒体动力学平衡来实现。方法随机将30只昆明小鼠分为空白对照组、缺血复供组及低、中、高剂量黄芩苷干预组。除空白对照组外,其余各组小鼠构建双下肢缺血再灌注损伤模型,并使用不同剂量黄芩苷溶液腹腔注射干预,缺血复供组使用生理盐水替代。采用苏木素-伊红(HE)染色检测各组骨骼肌损伤情况,检测各组骨骼肌组织线粒体分裂蛋白1(FIS1)、线粒体动力相关蛋白1(DRP1)、线粒体融合蛋白(Mfn)1、Mfn2的基因和蛋白表达水平,同时检测各组骨骼肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)水平。结果小鼠双下肢缺血再灌注损伤后,下肢骨骼肌出现明显损伤和炎症浸润。与空白对照组相比,其他各组骨骼肌组织FIS1、DRP1的基因和蛋白表达及MDA水平均明显升高(P<0.05),Mfn1、Mfn2的基因和蛋白表达及GSH、SOD水平均明显降低(P<0.05)。给予3种剂量黄芩苷溶液干预小鼠模型后,与缺血复供组比较,高剂量黄芩苷干预组DRP1基因表达明显下降(P<0.05),中、高剂量黄芩苷干预组的DRP1蛋白表达均明显下降(P<0.05),高剂量黄芩苷干预组GSH、SOD水平均明显升高(P<0.05),高剂量黄芩苷干预组MDA水平明显下降(P<0.05)。不同剂量黄芩苷干预组的FIS1基因、蛋白表达比较,差异均无统计学意义(P>0.05),不同剂量黄芩苷干预组Mfn1、Mfn2的基因及蛋白表达出现少量升高但差异均无统计学意义(P>0.05)。结论小鼠下肢骨骼肌缺血再灌注损伤后,下肢肌群发生氧化应激损伤,线粒体动力学失衡。黄芩苷对骨骼肌缺血再灌注损伤的抑制作用可能与减轻氧化应激损伤、抑制DRP1的表达有关。

中药有效成分干预运动性骨骼肌损伤的作用机制研究进展

运动性骨骼肌损伤(exercise-induced skeletal muscle damage,EIMD)属于运动医学科高发病率疾患之一,对患者日常生活和工作有较大影响。研究表明,中药有效成分包括皂苷类、多酚类、多糖类、黄酮类及其他异硫氰酸酯类、苯丙素类、羧酸类等活性物质可抑制实验动物及临床观察患者的炎症反应、氧化应激和线粒体自噬,促进肌卫星细胞增殖分化,调控核红细胞2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)/血红素氧合酶1(heme oxygenase-1,HO-1)、磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB/Akt)、磷酸化38丝裂原活化蛋白激酶(phosphorylation mitogen 38-activated protein kinase,p38 MAPK)等相关信号通路,促使受损的骨骼肌组织修复并加速修复进程。中药历史悠久,具有副作用小、多治疗靶点及价格实惠等优势,在EIMD的治疗中具有极大的潜力和应用前景。本文就近年来关于中药有效成分治疗EIMD的作用机制做一综述,以期为EIMD治疗和康复提供参考和依据。

不同强度运动对大鼠骨骼肌细胞凋亡的影响

通过比较不同强度运动对大鼠不同类型骨骼肌细胞凋亡的影响,研究氧自由基和线粒体摄取Ca2 + 在骨骼肌细胞凋亡中所起的作用,以探寻运动导致骨骼肌细胞凋亡的机制。采用成年雄性SD大鼠30只,随机分为安静对照组、中等强度运动组和大强度运动组。测定骨骼肌线粒体中的Ca2 +含量,观察凋亡肌细胞核。结果表明1)中等强度运动组的比目鱼肌的细胞凋亡率明显高于其他组;2 )电镜下观察到凋亡肌细胞核出现染色质凝集到核膜边缘,细胞核呈现不规则形态;3)中等强度力竭性运动后,比目鱼肌线粒体钙含量比对照组增加了5 3% (P<0 .0 5 ) ,其他组线粒体钙含量只有少量的增加,与对照组相比差异不具有显著性意义。结论线粒体内Ca2 +的大量积聚可能激活了细胞凋亡的启动程序,这使得中等强度力竭运动更易于导致慢肌细胞凋亡。