Study on Mechanism of Dendrobium officinale Kimura et Migo in Preventing and Treating Exercise-induced Muscle Damage(EIMD)in Rats

[Objectives]This study was conducted to observe the mechanism of Dendrobium officinale Kimura et Migo on gastrocnemius muscle in rats with exercise-induced muscle damage(EIMD).[Methods]The micro-injury model of skeletal muscle was established by treadmill training.Forty two SD rats were randomly divided into a control group,1,12 and 24 h exercise groups,D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group,and D.officinale 2 ml+24 h exercise group,with 6 rats in each group.Various D.officinale groups were given the drug once in the morning and once in the evening at a dose of 2 ml/time,a week in advance.Except for the quiet group,the samples were collected from the 1,12 and 24 h exercise groups after anesthesia following 1,12 and 24 h of exercise for the last time,respectively,and the D.officinale 2 ml+1 h exercise group,D.officinale 2 ml+12 h exercise group and D.officinale 2 ml+24 h exercise group were also sampled after anesthesia following 1,12 and 24 h of exercise for the last time,respectively.The contents of ATP,CK-MM and CK in rat serum were determined by enzyme-linked immunosorbent assay(ELISA).The histopathological changes of gastrocnemius muscle were observed by HE staining.PCR and Western-blot detection were carried out to analyze the effects of D.officinale on IGF-1 mRNA and protein expression in gastrocnemius muscle.[Results]Compared with the quiet group,the ATP contents in the serum of rats in the 1,12 and 24 h exercise groups significantly decreased(P<0.01),while the CK and CK-MM contents significantly increased(P<0.01).The expression of IGF-1 mRNA and protein in the gastrocnemius muscle tissue significantly increased(P<0.01).Compared with the 1 h exercise group,the ATP content and IGF-1 protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+1 h exercise group significantly increased(P<0.05),while the CK and CK-MM contents significantly decreased(P<0.01).Compared with the 12 h exercise group,the D.officinale liquid+12 h exercise group showed a significant increase in ATP content(P<0.01),significant increases in IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue(P<0.01),and significant decreases in CK and CK-MM contents(P<0.01).Compared with the 24 h exercise group,the ATP content and IGF-1 mRNA and protein expression in the gastrocnemius muscle tissue of the D.officinale liquid+24 h exercise group significantly increased(P<0.01),while the CK and CK-MM contents significantly decreased(P<0.01).From the pathological tissue morphology of the gastrocnemius muscle in rats with EIMD treated with D.officinale,it could be concluded that the gastrocnemius muscle of each exercise group was significantly damaged,and the damage was significantly alleviated after administration of D.officinale liquid.[Conclusions]The effects and mechanism of D.officinale on prevention and treatment of EIMD in rats might be related to the promotion of IGF-1 mRNA and protein expression in injured tissues by reducing ATP energy consumption,CK-MM and CK activity.

Single dose of intra-muscular platelet rich plasma reverses the increase in plasma iron levels in exercise-induced muscle damage:A pilot study

Background:Platelet rich plasma(PRP) therapy is widely used in enhancing the recovery of skeletal muscle from injury.However,the impact of intramuscular delivery of PRP on hematologic and biochemical responses has not been fully elucidated in exercise-induced muscle damage.The purpose of this investigation the effects of intramuscular delivery of PRP on hematologic and biochemical responses and recovery strategy muscle damage induced by high intensity muscle exercise(exercise-induced muscle damage,EIMD).Methods:Moderately active male volunteers participated in this study and were assigned to a control group(control,n = 6) and PRP administration group(PRP,n = 6).The subjects performed exercise with a load of 80% one repetition maximum(1RM) maximal voluntary contraction of the elbow flexors until point of exhaustion of the non-dominant arm was reached.The arms were treated with saline or autologous PRP post-24 h EIMD.Venous blood samples were obtained in the morning to establish a baseline value and 1–4 days post-exercise and were analyzed for serum ferritin,iron,iron binding capacity(IBC),creatinine kinase(CK),lactate dehydrogenase(LDH),aspartate aminotransferase(AST),and alanine aminotransferase(ALT).Results:The baseline levels of plasma iron,ferritin,IBC,CK,LDH,AST,and ALT were similar in both the control and PRP groups.However,24-h following exercise a significant increase in these parameters was observed in both groups between 1 and 4 days during the recovery period.Interestingly,PRP administration decreased plasma iron levels compared to the control on the second day post-exercise.Plasma IBC increased in PRP group from Days 2 to 4 post-exercise compared to the control group whilst PRP administration had no effect on plasma ferritin,CK,AST,ALT,or LDH.Conclusion:Acute exhaustive exercise increased muscle damage markers,including plasma iron,IBC,and ferritin levels,indicating muscle damage induced by exercise.PRP administration improves inflammation by reversing the increase in the iron levels post-exercise without displaying any myotoxicity and may have a role to play in the recovery of exercise-induced muscle damage.

Effect of Chronic Supplementation of Branched Chain Amino Acids on Exercise-Induced Muscle Damage in Trained Athletes

PURPOSE： Branched Chain Amino Acids （BCAA） has been considered an important nutritional strategy to improve skeletal muscle protein turnover in many conditions especially following exercise induced muscle damage. Exercise induced muscle damage （EIMD）, a phenomenon impairs muscle function and hampers athletic performance. The effects of consumption of BCAA for a chronic period （4 weeks） on EIMD in trained athletic population have never been explored. Therefore, the aim of the present study was to examine the effects of chronic consumption （4 weeks） of BCAA on indices of muscle damage elicited via a bout of damaging exercise in trained athletes. METHODS： Twenty trained males （20 road cyclists） aged 18-28 years were randomly assigned to two groups （BCAA and Placebo） （n = 10）. The damaging exercise consisted of 100 consecutive drop-jumps. Biochemical markers including creatine kinase （CK）, high sensitivity c reactive protein （hs-cRP） and myeloperoxidase （MPO）, isometric knee muscle strength, muscle soreness, aerobic capacity （WO2max） and heart rate （HR） were measured. RESULTS： Differences were observed in pre-and post-supplementation periods among all the participants with mean height and weight values of 168.57 （4.5） cm and 61.74 （4.55） kg respectively as calculated by the anthropologist randomly allocated to the two groups in all tested parameters indicating the effectiveness of BCAA in attenuating muscle damage and enhancing muscle recovery with chronic consumption when compared to placebo, however in contrast to our expectations based on symptoms and our clinical judgment during the study statistically significant difference （P 〈 0.05） were noticed with biochemical indices only. CONCLUSION： Our findings suggest that chronic BCAA supplementation proved to be an effective meansof reducing muscle damage, enhancing muscle protein synthesis and recovery following EIMD as compared to placebo in well trained athletic population.

Effects of exercise-induced skeletal muscle damage and ultrastructure of muscle

Micro- injury （exercise-induced muscle damage, EIMD） will cause a temporary decline in muscle function, if not handled properly, it could cause more serious injury or overtraining, and even lead to the end of the athletes ＇ sports life. However, some studies have shown that an appropriate period of eccentric exercise training resulted in EIMD while promoted heart muscle fiber hypertrophy and corresponding muscle growth faster than exercise training, and there are the typical ＂ repetitive training effect＂ , ie after a period of the EIMD recovery, the muscle＇ s injury or delayed onset muscle soreness （DOMS） caused by the same movement is significantly reduced. So its deep study could help to guide the athlete to avoid or mitigate the negative effects which brought by EIMD, while could help to further clarify the process of the body to adapt to exercise training or mechanism.

Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms： Roles of androgen, IGF-1, and IGF binding protein-3

Purpose: To investigate the effects of Tribulus terrestris(TT) extracts on muscle mass, muscle damage, and anaerobic performances of trained male boxers and its mechanisms: roles of plasma androgen, insulin growth factor 1(IGF-1), and IGF-1 binding protein-3(IGFBP-3).Methods: Fifteen male boxers were divided into exercise group(E, n = 7) and exercise plus TT group(E + TT, n = 8). The 2 groups both undertook3-week high-intensity and 3-week high-volume trainings separated by a 4-week rest. TT extracts(1250 mg/day) were orally administered by boxers in E + TT group. TT extract compositions were detected by UHPLC–Q-TOF/MS. Before and at the end of the 2 trainings, muscle mass, anaerobic performance, and blood indicators were explored.Results: Compared with E group, decreases of plasma CK(1591.5 ± 909.6 U/L vs. 2719.9 ± 832.5 U/L) and IGFBP-3(3075.5 ± 1072.5 ng/m L vs. 3950.8 ± 479.3 ng/m L) as well as increases of mean power(MP, 459.4 ± 122.3 W vs. 434.6 ± 69.5 W) and MP/body weight(MP/BW, 7.5 ± 0.9 W/kg vs. 7.1 ± 1.1 W/kg) were detected in E + TT group after a high-intensity training. For high-volume training, reduction of IGFBP-3(2946.4 ± 974.1 ng/m L vs. 3632.7 ± 470.1 ng/m L) and increases of MP(508.7 ± 103.2 W vs. 477.8 ± 49.9 W) and MP/BW(8.2 ± 0.3 W/kg vs.7.5 ± 0.9 W/kg) were detected in E + TT group, compared with E group. Muscle mass, blood levels of testosterone, dihydrotestosterone(DHT),and IGF-1 were not signifiantly changed between the 2 groups.Conclusion: Taking 1250 mg capsules containing TT extracts did not change muscle mass and plasma levels of testosterone, DHT, and IGF-1 but significantly alleviated muscle damage and promoted anaerobic performance of trained male boxers, which may be related to the decrease of plasma IGFBP-3 rather than androgen in plasma.

Protective Effect of ATP on Skeletal Muscle Satellite Cells Damaged by H_2O_2

This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H2O2 in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups： normal group, model group（cells treated with 0.1 mmol/L H2O2 for 50 s）, protection group（cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H2O2 for 50 s）, proliferation group（cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h）. MTT assay, FITC＋PI＋DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H2O2 treatment（P〈0.01）. Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H2O2： the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells（P〈0.01） and decrease the number of the Bax-positive cells（P〈0.01）. It was concluded that ATP could protect skeletal muscle satellite cells against H2O2 damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.

Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms

Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of highfrequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1-and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus(EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca2+-ATPase(SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase(nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated intracellular resting Ca2+ concentration([Ca2+]i) in unloaded soleus muscles. High [Ca2+]i activated calpain-1 which induced a higher degradation of desmin. Desmin degradation may loose connections between adjacent myofibrils and further misaligned Z-disc during repeated tetanic contractions. Passive stretch in unloaded muscle could preserve the stability of sarcoplasmic reticulum Ca2+ release channels by means of keeping nNOS activity, and decrease the enhanced protein level and activity of calpain to control levels in unloaded soleus muscles. Therefore, passive stretch restored normal appearance of Z-disc and resisted in part atrophy of unloaded soleus muscles. The above results indicate that enhanced fatigability of high-frequency tetanic contraction is associated to the alteration in K+ channel characteristics, and elevated SERCA activity and slow to fast transition of myosin heavy chain(MHC) isoforms increases fatigability of intermittent tetanic contraction in atrophic soleus muscle. The sarcomeric damage induced by tetanic contraction can be retarded by stretch in atrophic soleus muscles.

Real-time surface electromyography in Parkinson's disease patients during exercise-induced muscle fatigue

To explore the mechanisms underlying exercise-induced local muscle fatigue in patients with idiopathic Parkinson＇s disease （PD）,we used surface electromyography to record myoelectric signals from the tibialis anterior muscle during isometric contraction-induced fatigue until exhaustion.The results revealed no significant differences between patients with idiopathic PD and healthy controls in maximum voluntary contraction of the tibialis anterior muscle.The basic characteristics of surface electromyography were also similar between the two groups.The duration of isometric contraction at 50% maximum voluntary contraction was shortened in PD patients.In addition,PD patients exhibited a stronger increase in mean square amplitude,but a weaker decrease in median frequency and mean power frequency compared with healthy controls during isometric contraction.The skeletal muscles of PD patients revealed specificity of surface electromyography findings,indicating increased fatigability compared with healthy controls.

Clemastine in remyelination and protection of neurons and skeletal muscle after spinal cord injury

Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.

Genotoxicity and Reduced Heat Shock Protein 70 in Human Airway Smooth Muscle Cells Exposed to Cigarette Smoke Extract

Cigarette smoke is associated with the development of several diseases, such as chronic ob- structive pulmonary disease （COPD）. The purpose of this study was to investigate genotoxicity and heat shock protein 70 （Hsp70） in human airway smooth muscle cells （HASMCs） exposed to cigarette smoke extract （CSE）. HASMCs was exposed to CSE with different doses for 24 h. The level of 8-hydroxydeoxyguanosine （8-OHdG） was determined by using HPLC-ECD, the DNA damage was ana- lyzed by using comet assay, and apoptosis was examined by using Annexin-FITC/PI staining. The pro- duction of Hsp70 after CSE stimulation was tested. Results indicated that CSE significantly increased the level of 8-OHdG, DNA damage and cell apoptosis, and reduced the production of Hsp70. In par- ticular, levels of Hsp70 were inversely correlated with 8-OHdG, DNA damage and cell apoptosis. It was concluded that cigarette smoke induced genotoxicity and decreased the production of cell protective protein Hsp70, which may contribute to the development of some airway diseases.

Diagnostic value of orbicularis oculi muscle electromyography in functional epiphora

BACKGROUND Functional epiphora is a clinical condition which is not due to an anatomic defect.Most studies agree that it involves the action of the orbicularis oculi muscle,particularly its deeper segment(Horner’s muscle),but the exact mechanism is not clear.AIM To evaluate the orbicularis oculi muscle in functional epiphora patients using electromyography(EMG).METHODS A total of 8 Chinese patients(16 eyes)with functional epiphora were enrolled in this study,and ten volunteers(10 eyes)were included as normal controls.Five epiphora patients(five eyes)with facial palsy served as positive controls.Quantitative EMG was performed in the deeper segment of orbicularis oculi muscle.The average duration of each EMG waveform was measured.RESULTS The average duration of EMG waveforms in the normal control group,the functional epiphora group,and the facial palsy group were 6.39±0.73 ms,9.39±1.32 ms and 11.2±1.42 ms,respectively.The duration of EMG waveforms was significantly longer in the functional epiphora group than in the normal control group(P<0.05),and shorter than that in the facial palsy group(P<0.05).CONCLUSION These data indicate the presence of neurogenic orbicularis oculi muscle damage in epiphora patients,which may be the cause of functional epiphora.The etiology of neurogenic damage in the orbicularis oculi muscle requires further investigation.

Age-Associated Changes in Skeletal Muscle Regeneration: Effect of Exercise

Aim of the present short review is to provide a comprehensive update on age-associated skeletal muscle damage, regeneration, and effect of endurance and resistance type of exercise training on muscle regeneration. Decrease in muscle quantity and quality leads to disability in the aging population. The degradation rate of muscle proteins during aging increased about two times, and muscle strength and motor activity decreased at the same time. Aging induced sarcopenia is a result of decreased synthesis and increased degradation of muscle proteins, which leads to the slower turnover rate of these proteins, especially contractile proteins, and this, in turn, leads to the decrease in muscle strength. Muscle damage is mainly caused by excessive strain in contracting fibre and aging muscle is particularly sensitive to it. The decreased synthesis and increased degradation rate of contractile proteins are in accordance with the increase destructive processes in muscle and lead to the decrease in the regeneration capacity and development of sarcopenia in the elderly. Exercise training increases muscle mass, oxidative capacity, contracile quality, regeneration capacity and via this, physiological functioning of skeletal muscle is improved in the elderly.

β-羟基-β-甲基丁酸对集训期间跆拳道运动员肌肉的保护

[目的]探究跆拳道运动集训期间补充β-羟基-β-甲基丁酸(HMβ)对肌肉保护的影响。[方法]招募选取自愿参与试验的18名跆拳道专项队二级以上男性受试者,随机分为试验组与对照组(各9人)。试验组周一至周六每日上、下午训练前、后分4次(与运动间隙超过30 min),冲服添加HMβ功能成分的运动奶粉各1袋(25 g/袋,HMβ添加量为500 mg/袋),对照组摄入等量市售普通奶粉。干预前、后及每周一晨采集血样分析生化指标的变化情况,并进行试验前后跆拳道专项能力的定量测试。[结果]相比于对照组,试验组干预后促炎因子白介素-6未见明显变化,血浆谷氨酰胺水平显著提升(P<0.05),血浆甘氨酸水平未见明显下降;试验组干预后肌红蛋白显著下降(P<0.05),血清总胆固醇、甘油三酯及低密度脂蛋白胆固醇水平均显著低于对照组(P<0.05),血尿素氮降幅小于对照组;试验组20 s原地提膝次数及30 s收腹跳次数均有提升,且增幅均超过对照组。[结论]训练期间补充HMβ能降低炎症程度、改善免疫功能、维持肌细胞膜稳定性、提高氮存量并强化肌肉重塑能力而发挥保护功能,提高肌肉对训练的适应性,以保障其竞技状态。

虾青素通过mTOR-ULK1自噬通路对大鼠运动性骨骼肌损伤影响的研究

目的:基于AMPK/mTOR/ULK1通路探究虾青素对大鼠运动性骨骼肌损伤(EIMD)的影响。方法:健康雄性SD大鼠随机分为对照组(C)、运动组(E)、虾青素组(M)、运动+虾青素组(EM)、运动+AICAR(5-氨基-1-核糖基咪唑-4-甲酰胺磷酸盐组)组(EA)、运动+虾青素+AICAR组(EMA)、运动+虾青素+MHY1485组(EMM),每组10只。M、EM、EMA、EMM组灌胃虾青素;C、E组灌胃大豆油;EA、EMA组注射AICAR;EMM组注射MHY1485;E、EM、EA、EMA、EMM组进行力竭运动,其余组安静饲养。运动结束后,采用HE染色观察大鼠比目鱼肌的组织病理变化;ELISA法检测血清MDA、SOD、IL-6、IL-1β、CK和FINS含量;RT-PCR法检测比目鱼肌相关指标的mRNA表达;Western blot法检测比目鱼肌AMPK/mTOR/ULK1自噬通路磷酸化水平及凋亡相关蛋白表达;检测大鼠FBG和LA水平,计算ISI和HOMA-IR;此外,通过中介效应分析探究LA、MDA、IL-6和IL-1β在EIMD及ISI中的作用。结果:E组大鼠血清MDA、IL-6、IL-1β、CK、LA、FBG和FINS含量、HOMA-IR明显高于C组,SOD含量和ISI明显低于C组;大鼠比目鱼肌p-AMPK Thr172、p-mTOR Ser2448、p-ULK1 Ser555和p-ULK1 Ser757蛋白表达、P62基因和蛋白表达均明显高于C组,LC3-II蛋白表达、ILC3-II/LC3-I和BCL2/BAX明显低于C组。虽然,给力竭运动大鼠灌胃虾青素或注射AICAR可逆转上述改变,且与EA和EM组相比,EMA组逆转效果更加明显,但是,给力竭运动大鼠施加虾青素及MHY1485的双重干预则明显阻断了虾青素对EIMD的改善作用。此外,MDA、IL-6和IL-1β在LA导致的EIMD及ISI下降中发挥了部分中介效应。结论:力竭运动可造成EIMD,其发病机制涉及乳酸堆积、氧化应激、炎症反应及细胞凋亡等,此时,胰岛素抵抗增加,肌细胞对葡萄糖的摄取与利用减少,这将上调骨骼肌mTOR活性,抑制自噬通量,加剧骨骼肌损伤。而虾青素干预可调控mTOR-ULK1自噬通路以缓解EIMD,且虾青素与AICAR的联合作用对改善EIMD更有益。

内皮微粒包裹的miR-204-3p介导川崎病血管炎性损伤的机制探讨

目的 探讨内皮微粒(EMP)包裹的miR-204-3p介导川崎病(KD)血管炎性损伤的作用机制。方法 2016年4月至2021年3月,58例KD患者和50例对照组入选本研究。其中,18例KD患者伴有冠状动脉瘤(CAA),其余为无冠状动脉瘤(NCAA)。分离各组血清样品中EMP,并进行全基因组miRNA测序。在体外试验中,将VSMC或预转染miR-204-3p模拟物(AgomiR-204-3p)、miR-204-3p抑制剂(AntagomiR-204-3p)的VSMC与各组EMP共培养。结果 通过全基因组miRNA测序以及RT-qPCR分析证实miR-204-3p在KD EMP中显著增加,并且EMP中miR-204-3p水平根据冠状动脉病理严重程度显著降低,顺序为NCAA>SCAA>MCAA>GCAA。与对照组EMP共培养相比,VSMC与NCAA EMP共培养48 h后增殖率显著降低(P<0.05),VSMC分化标志物(ACTA2和CNN1)表达显著增加(P<0.05),去分化标志物(OPN和PDGFRβ)表达显著降低(P<0.05)。双荧光素酶报告基因检测证实,EMP中miR-204-3p在功能上靶向VSMC中的PDGFRβ。在与NCAA EMP孵育的VSMC中,使用AntagomiR-204-3p可显著降低分化标记物(ACTA2和CNN1)的表达,并增加去分化标记物(OPN和PDGFRβ)的表达。在与CAA EMP孵育的VSMC中,给予AgomiR-204-3p显著增加分化标记物的表达,并降低去分化标记物的表达。结论 EMP将miR-204-3p转移到VSMC并通过靶向PDGFRβ部分介导KD血管炎性损伤。因此,靶向miR-204-3p-PDGFRβ轴可能为KD诱导的血管病变提供新的治疗选择。

LncRNA NORAD通过miR-513b-5p/GREM1轴调节颅内动脉瘤血管平滑肌细胞增殖、迁移、侵袭和凋亡的作用机制

目的:探讨长链非编码RNA DNA损伤诱导的非编码RNA(LncRNA NORAD)通过miR-513b-5p/GREM1轴调节颅内动脉瘤血管平滑肌细胞(VSMC)增殖、迁移、侵袭和凋亡的机制。方法:采用实时荧光定量聚合酶链式反应(PCR)法检测人颅内动脉瘤组织和正常组织中LncRNA NORAD、miR-513b-5p及GREM1表达。体外分离培养人VSMC,随机分为对照组、LncRNA NORAD siRNA组、miR-513b-5p mimics组、共转染(LncRNA NORAD siRNA+miR-513b-5p inhibitor)组、共转染阴性对照(LncRNA NORAD siRNA阴性对照+miR-513b-5p inhibitor阴性对照)组,分组转染后,采用实时荧光定量PCR法检测各组细胞LncRNA NORAD、miR-513b-5p及GREM1 mRNA表达;采用细胞计数试剂盒(CCK-8)和免疫荧光染色检测各组细胞增殖情况;采用Hoechst 33342染色和免疫荧光染色检测各组细胞凋亡情况;采用细胞划痕实验和Transwell实验检测各组细胞迁移、侵袭情况;采用免疫印记实验检测各组细胞上皮间充质转化(EMT)标志蛋白神经钙黏素(N-cadherin)、E-钙黏素(E-cadherin)、波形蛋白(Vimentin)表达;采用双荧光素酶报告实验分析VSMC中LncRNA NORAD对miR-513b-5p、miR-513b-5p对GREM1的靶向调控。结果:与正常组织比较,颅内动脉瘤组织LncRNA NORAD、GREM1 mRNA表达明显升高(P<0.05),miR-513b-5p表达明显降低(P<0.05)。与对照组比较,LncRNA NORAD siRNA组、miR-513b-5p mimics组细胞GREM1 mRNA表达、增殖率、Ki67阳性率、迁移率、侵袭数及N-cadherin、Vimentin蛋白表达降低(P<0.05),miR-513b-5p表达、凋亡率及Bax/Bcl-2、E-cadherin蛋白表达升高(P<0.05);共转染阴性对照组各指标差异无统计学意义(P>0.05)。与LncRNA NORAD siRNA组比较,共转染组细胞GREM1 mRNA表达、增殖率、Ki67阳性率、迁移率、侵袭数及N-cadherin、Vimentin蛋白表达升高(P<0.05),miR-513b-5p表达、凋亡率及Bax/Bcl-2、E-cadherin蛋白表达降低(P<0.05)。结论:敲低LncRNA NORAD可通过上调miR-513b-5p表达而降低GREM1表达,从而抑制VSMC增殖与侵袭迁移,并促使其凋亡。

肌萎缩侧索硬化症发病机制及药物研究进展

肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)是一种病因未明的运动神经元疾病,同时累及上、下运动神经元,患者表现出进行性加重的肌肉萎缩、无力、瘫痪,最终死于呼吸衰竭。ALS具有进展快、致死率高的特点,该疾病异质性强,发病机制研究不明确,缺乏有效的治疗药物。因此,探究ALS疾病病理机制、助力新药研发,解决未被满足的临床需求具有重大的科学价值及社会意义。该文针对ALS的发病机制及治疗药物的研究现状进行综述,希望为ALS药物研发提供思路。

二氢杨梅素对运动性骨骼肌损伤的保护作用及机制研究

目的探讨二氢杨梅素(dihydromyricetin,DHM)对运动训练后小鼠骨骼肌损伤的保护作用及潜在机制。方法将成年雄性C57BL/6J小鼠随机分为安静对照组(CG)、运动组(EG)、二氢杨梅素(100mg/kg·d)+运动组(DHM组)。干预期4周,同时进行运动训练,每天1小时。训练结束后的次日,EG组和DHM组进行一次坡度为0、速度为18 m/min、持续90 min的跑台运动。运动结束后24小时按组别取材,测定血清肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactate dehydrogenase,LDH)和总超氧化物歧化酶(total superoxide dismutase,T-SOD)活性、丙二醛(malondialdehyde,MDA)含量和骨骼肌线粒体酶复合体Ⅰ和Ⅱ的活性,观察骨骼肌病理学组织形态变化。免疫印迹法(Western blot)检测线粒体功能相关通路的蛋白表达。结果与EG组相比,DHM组小鼠骨骼肌形态改变和线粒体损伤明显减轻。DHM显著抑制了运动后骨骼肌损伤的标志物CK和LDH及脂质过氧化水平,提高了骨骼肌T-SOD活性。Western blot结果显示,DHM显著增加小鼠骨骼肌沉默调节蛋白3(SIRT3)、雌激素相关受体α(EERα)和过氧化物酶体增殖物激活受体-γ共激活因子-1α(peroxisome proliferator-activated receptor gamma coactivator-1 alpha,PGC-1α)的表达。结论DHM有助于减轻小鼠运动性骨骼肌损伤,其机制可能是DHM可激活肌肉SIRT3信号通路,促进大强度运动后骨骼肌线粒体结构和功能的恢复。

补充植物蛋白对运动能力的影响

肉类和其他动物来源蛋白质一直被视为运动员和健身人群饮食中不可或缺的组成部分。近年来,植物蛋白因其对环境和健康的积极作用越来越受到欢迎。但相较于动物蛋白,我国对植物蛋白应用仍处于初步阶段,植物蛋白的补充对人体运动能力影响的相关研究也相对较少。该文简述了植物蛋白的营养特点,探讨了阻力、耐力训练中补充植物蛋白质对肌肉力量及质量、瘦体重、运动表现以及肌肉损伤和恢复等方面的作用,指出了植物蛋白改善运动能力的有效剂量和其他影响因素,以期为植物蛋白在运动领域的研究、开发和应用提供依据。