AMPK在机体骨骼肌运动代谢适应方面的研究进展

腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)作为机体细胞的"能量感受器",可通过激活其下游靶蛋白调节组织细胞糖、脂代谢过程。运动适应涉及机体多个系统和器官,其中骨骼肌在机体对运动产生的代谢适应方面的作用最为明显。运动作为对机体的一个刺激可活化组织细胞AMPK,本文将针对AMPK在机体组织对运动产生代谢适应方面的最新研究进展加以综述,以期为阐明运动防治代谢性疾病的机制提供理论依据。     

运动对骨骼肌基因表达的表观遗传调控作用

DNA甲基化、组蛋白修饰和miRNA表达调控是表观遗传调控的3种重要方式,其在基因表达调控中发挥着关键作用。适当运动有益于身心健康。骨骼肌作为运动的主体组织,运动可以提高其代谢能力,改善其线粒体生物学功能,调控肌纤维类型转化,增加骨骼肌力量。近年来越来越多的研究表明,表观遗传调控在机体适应运动过程中发挥着重要作用,DNA甲基化、组蛋白修饰和miRNA表达调控等表观遗传调控方式通过调控骨骼肌基因表达来改变骨骼肌代谢能力、线粒体生物学功能和肌纤维类型,从而适应运动变化。本文对近年来运动对骨骼肌基因DNA甲基化、组蛋白修饰和相应miRNA表达调控等3种表观遗传调控方式的研究现状进行了综述,以期为进一步研究运动改善机体机能和健康提供参考。     

鼎突多刺蚁热适应及运动行为的热依赖性

将鼎突多刺蚁(Polyrhachis vicina)分别置于15、20、25和30℃的恒温恒湿培养箱内,对其热适应及运动行为的热依赖性进行了研究。驯化2周后,采用温度梯度仪测量其热适应参数,并选用停顿频率(PF)、疾跑速度(SS)和最大持续运动距离(MDCCL)来衡量其运动能力。结果表明,驯化温度对鼎突多刺蚁的热适应和运动行为有极显著影响(P<0.01)。最适温度(PT)、临界低温(CLT)、临界高温(CHT)随驯化温度(AT)的升高而增大,最终适温为30.54℃,临界低温不低于3℃,临界高温不高于45℃;经过高温驯化的鼎突多刺蚁的运动能力显著大于经过低温驯化的个体运动能力,驯化温度与疾跑速度、最大持续运动距离呈显著的正相关,而与停顿频率呈极显著的负相关。     

线粒体在运动诱导骨骼肌适应过程中的应答机制

运动训练通过诱导骨骼肌适应提高运动机能和健康水平。在此过程中,线粒体具有显著的可塑性,不断地重塑自身的网络结构,并对骨骼肌收缩所引发的一系列信号刺激做出相应的应答反应,以适应骨骼肌对代谢的需求。当线粒体功能失调时,机体通过特定的细胞内系统对这类线粒体进行清除及再利用。因此,运动适应过程中线粒体的应答包括线粒体数量和质量的协同调控。本文着重关注骨骼肌适应中的线粒体质量控制应答,并总结目前对运动调节这些应答机制的理解。     

东方田鼠的游泳行为和能力

东方田鼠(Microtus fortis)是一种栖息于湿地生境的小型哺乳动物,为了解其水生运动适应,作者在实验室内观察和测试了该鼠的游泳行为、皮毛防水性能和长时间游泳能力。结果发现,东方田鼠主要在水面游泳,亦能潜水,游泳姿势是狗刨式,并主要以后肢交替划水提供推进力,速度约为0.37 m/s。在20℃水温条件下,东方田鼠皮毛表现出良好的防水性能,且防水性能与其年龄及体重均存在极显著的负相关关系(P 0.01,R~2=0.805);东方田鼠具有平均约持续5 h以上的长时间游泳能力,且长时间游泳能力与其皮毛防水性能存在极显著的正相关关系(P 0.01,R~2=0.682);上述两项指标性别差异显著。这表明,东方田鼠有较强的水中运动能力和长时间游泳能力,具有水生运动方面的适应性进化,有利于其在沼泽等栖息地的生存。     

热驯化对鼎突多刺蚁热适应和运动行为的影响

为比较恒温和变温驯化对鼎突多刺蚁（Polyrhachis vicina Roger）热适应和运动行为的影响,将鼎突多翅蚁分别在15℃恒温和13.4～21.6℃变温下进行驯化,定量分析两种驯化温度对鼎突多翅蚁热适应和运动行为的影响.结果表明,恒温和变温驯化对鼎突多刺蚁的最适温度、逃避高温、运动中的停顿频率、疾跑速度、最大持续运动距离均有显著影响（p＜0.01）,而对逃避低温的影响不显著（p=0.343）;变温驯化后鼎突多刺蚁的最适温度仅有一个峰值,这不符合最适性模型的预测;恒温和变温驯化下鼎突多刺蚁的疾跑速度与最大持续运动距离都呈显著的正相关（分别为p=0.017和p＜0.001）,且经过变温驯化的鼎突多刺蚁的运动能力明显强于恒温驯化下个体的运动能力.     

蛋白激酶C在运动预适应诱导的心肌保护效应中的作用机制

多项研究证实运动预适应(EP)可以为心脏提供心肌保护作用,本研究推测其心脏保护机制可能通过蛋白激酶C (PKC)介导。本研究将100只8周龄成年雄性Sprague-Dawley大鼠随机分为5组,即对照组(Control组)、力竭运动组(EE组)、运动预适应组(EP组)、运动预适应+力竭运动组(EP+EE组)和蛋白激酶C抑制剂白屈菜红碱(chelerythrine, CHE)+运动预适应+力竭运动组(CHE+EP+EE组),每组20只。分别检测各组大鼠的跑动距离和心脏损伤标志物cTnI和NT-proBNP水平,应用HBFP染色分析大鼠心脏损伤程度,采用RT-PCR、原位杂交和Western blotting检测大鼠PKCε和p-PKCεSer729的表达。研究显示,EE组的跑动距离显著低于EP+EE组和CHE+EP+EE组。EE组血清cTnI和NT-proBNP水平显著高于Control组。与EE组相比,EP+EE组血清c TnI和NT-proBNP水平均显著下降,而CHE+EP+EE组显著高于EP+EE组。HBFP染色分析显示,与Control组相比,EE组的HBFP染色阳性面积显著增加。此外,EP+EE组和CHE+EP+EE组的阳性面积均显著低于EE组,但CHE+EP+EE组显著高于EP+EE组和Control组。EE组的PKCε和p-PKCεSer729的mRNA和蛋白相对表达量均显著低于Control组,但EP+EE组和CHE+EP+EE组PKCε的表达水平显著高于EE组,且CHE+EP+EE组显著低于EP+EE组。本研究推测运动预适应对心脏的保护作用可能与蛋白激酶C的上调有关。     

短期和长期运动预适应对力竭大鼠心肌损伤的保护作用

目的：研究短期和长期运动预适应对心肌细胞凋亡保护中发挥的作用及机制。方法：48只雄性SD大鼠随机分为对照组（C）、力竭组（E）、短期运动预适应组（S-EP）、长期运动预适应组（L-EP）。短期和长期运动预适应分别进行3 d和3周的反复间歇游泳训练方案。光镜下观察心肌细胞的结构改变;ELISA方法检测血清中缺血修饰白蛋白（IMA）、磷酸肌酸同工酶（CK-MB）含量;实时荧光定量PCR和Western blot方法检测心肌组织中TNF-α、Caspase-8、Caspase-3基因和蛋白表达;采用DNA原位末端标记（TUNEL）法观察心肌细胞的凋亡情况。结果：与C组相比,E组心肌细胞损伤严重,血清IMA、CK-MB含量及心肌组织中TNF-α、Caspase-8、Caspase-3 mRNA和蛋白表达升高（P<0.05）;与E组相比,S-EP组血清CK-MB及心肌TNF-α、Caspase-8mRNA明显降低（P<0.05）,而蛋白表达无统计学差异,血清IMA及Caspase-3 mRNA和蛋白均下降不明显,无统计学意义（P>0.05）,L-EP组血清IMA、CK-MB含量及心肌TNF-α、Caspase-8、Caspase-3 mRNA及蛋白明显降低,有统计学意义（P<0.05）;与S-EP组相比,L-EP组血清IMA、CK-MB含量及TNF-α、Caspase-8、Caspase-3 mRNA和蛋白明显下降,有统计学意义（P<0.05）。E组心肌细胞凋亡明显,S-EP组和L-EP组均能抑制凋亡,且L-EP组与S-EP组相比心肌凋亡明显减少。结论：短期和长期运动预适应均可减轻力竭后的心肌损伤,但短期运动预适应并未改变Caspase蛋白酶的表达,长期运动预适应明显抑制Caspase-8、3 mRNA表达,减少蛋白合成,从而发挥心肌保护效应,故长期运动预适应在抑制心肌细胞凋亡方面较短期运动预适应更强。     

递增负荷运动对大鼠下丘脑弓状核ACh、DA、NA、AD的影响

目的:在大鼠进行6周递增负荷运动的过程中,获得下丘脑弓状核乙酰胆碱(ACh)、多巴胺(DA)、去甲肾上腺素(NA)、肾上腺素(AD)阳性神经元表达的变化信息,观察其变化特征,探讨其变化规律及相互关系。方法:通过免疫组化技术测定ACh、DA、NA、AD的表达。结果:在一次负荷运动后即刻和恢复期,ACh变化不明显(P>0.05),DA运动后即刻变化不大,运动后3 h下降(P<0.05),NA变化表现不一(P>0.05),AD运动后明显升高且恢复期仍处于较高水平(P<0.05);在6周运动训练过程中,ACh有降低趋势但变化不明显(P>0.05),DA变化不明显(P>0.05),AD先增加而后逐渐回降(P<0.05),NA可能与AD的变化一致。结论:在一次负荷运动中,下丘脑弓状核ACh、NA、AD与运动应激HPA轴的兴奋有密切关系,AD是促进HPA轴兴奋的主要因素之一。在6周运动训练过程中,HPA应激轴的兴奋可能在运动适应初期由NA、AD,后期由ACh起主导作用。     

植物根源逆境信使及其产生和传输

植物不仅仅是恶劣环境的被动受害者 ,而且它也具有对环境变化快速感知和主动适应的能力 ,逆境信息传递就是其适应不良环境的重要策略。本文主要介绍了环境胁迫下 ,调控植物地上部的根源信使、信使的产生和传输以及气孔运动对根源信使的响应机制等方面的研究进展。     

肥厚型心肌病患者运动血压反应异常的两类表现及其相关因素分析*

目的: 运动血压反应不足及运动后恢复期血压降低是肥厚型心肌病（HCM）患者常见的异常表现,本研究的目的是分析HCM患者这两类异常血压反应表现的相关因素及其与心肺运动功能的关系。方法: 回顾性研究2018年4月至2020年1月期间在阜外医院功能检测中心行心肺运动试验（CPET）的HCM患者219例。111例行CPET的性别、年龄匹配的正常体检者作为正常对照组。比较正常对照组与HCM组的CPET运动血压反应。将HCM患者分为运动血压反应正常组及运动血压反应不足组,以及运动后血压正常组及运动后恢复期血压降低组,分别比较上述两类运动血压反应异常者的临床情况及CPET功能指标。结果: 与正常对照组相比,HCM患者运动血压反应不足（8.7%比1.8%,P=0.016）及运动后恢复期血压降低（6.8%比0.0%,P=0.003）的发生率显著升高。在HCM患者中,与运动血压反应正常者相比,运动血压反应不足的HCM患者更多合并冠心病（P=0.029）、肺动脉高压（P=0.002）及房颤/房扑（P=0.036）;与运动后血压正常者相比,运动后恢复期血压下降的HCM患者静息流出道压差（P=0.017）更高,合并流出道梗阻比例（P=0.015）、合并收缩期二尖瓣前移现象（P=0.022）及左室射血分数（P=0.043）更高。经过Logistic多元回归分析,运动血压反应不足的独立相关因素为冠心病（β=1.519,P=0.013）、肺动脉高压（β=2.292, P=0.000）。而运动后恢复期血压下降仅与左室流出道压差有独立的相关性（β=0.018, P=0.005）。运动血压反应不足的HCM患者峰值摄氧量（P=0.003）、峰值心率（P=0.014）及心率储备（P=0.003）更低,NT末端B型脑钠肽前体（P=0.019）及二氧化碳通气当量斜率（P=0.000）更高。运动后恢复期血压下降与各种心肺功能指标均无相关性。结论: HCM运动血压反应不足及运动后恢复期血压降低的发生率均较正常人群显著升高。HCM患者运动血压反应不足与合并冠心病和肺动脉高压有显著的独立相关性,而运动后血压下降仅与左室流出道压差独立相关。运动血压反应不足的HCM患者心肺运动功能降低,而运动后恢复期血压降低与心肺运动功能无显著相关性。     

Effects of aerobic exercise on metabolic syndrome improvement in response to weight reduction

Objective: The objective was to test effects of aerobic exercise training on metabolic syndrome (MetSyn) improvement in response to weight reduction. Research Methods and Procedures: A total of 459 overweight and obese women (age, 49 ± 9 years; BMI, 28 ± 3 kg/m²) were recruited for a baseline examination to test the relationship between cardiorespiratory fitness and metabolic syndrome prevalence; among these, 67 subjects with MetSyn were treated with 14‐week weight‐loss programs, which included low‐calorie diet and aerobic exercise. The MetSyn was defined according to the Examination Committee of Criteria for “Metabolic Syndrome” in Japan. Maximal oxygen uptake (V?o _2max) during a maximal cycling test was measured as an index of cardiorespiratory fitness at baseline and after the intervention. Results: In the baseline examination, age‐ and BMI‐adjusted odds ratios for MetSyn prevalence in the low, middle, and upper thirds of V?o _2max were 1.0 (referent), 0.50 (95% confidence interval, 0.26 to 0.95), and 0.39 (95% confidence interval, 0.14 to 0.96), respectively (linear trend, p = 0.02). The adjusted odds ratios for MetSyn improvement in the two interventions with diet alone and diet plus exercise were 1.0 and 3.68 (95% confidence interval, 1.02 to 17.6; p = 0.04), respectively. Discussion: These results suggest that adding aerobic exercise training to a dietary weight‐reduction program further improves MetSyn (adjusted odds ratio, 3.68) in obese women, compared with diet alone. Further studies on an association between V?o _2max change and MetSyn improvement are needed.     

肌酸提高运动能力的作用

介绍了肌酸在机体的分布与合成及其在肌肉能量代谢中的作用。综述了补充肌酸对提高体内肌酸含量和运动能力的作用 ,并介绍了肌酸提高运动能力作用的机制研究情况     

Effects of acute exhaustive physical exercise upon glutamine metabolism of lymphocytes from trained rats

Transitory immunosupression is reported after intense exercise, especially after an increase in training overload and in overtraining. The influence of intense exercise on plasma hormones and glutamine concentration may contribute to this effect. However, the effect of such exercise-induced changes upon lymphocyte and glutamine metabolism is not known. We compared glutamine metabolism in lymphocytes in sedentary (SED) and trained rats. Rats from the moderate group (MOD) swam for 6 weeks, 1 h/day, in water at 32+/-1 degrees C, with a load of 5.5% body weight attached to the tail. Animals from the exhaustive group (EXT) trained like MOD, with training increasing to 3 times 1 h a day during the last week, with 150 min rest between each bout. Animals were killed immediately after the last training bout. We observed reduced concentrations of plasma glucose (p<0.05), glutamine (p<0.05), glutamate (p<0.05) in EXT compared to SED. In MOD, decreases in glutamine (p<0.05) were observed. Analyzing lymphocyte metabolism, we observed an increase in lactate production and glutamine consumption (p<0.05) in MOD (p<0.05) compared to SED and a decrease in glutamine consumption (p<0.05) and aspartate production in EXT. An increase in the proliferative response of lymphocytes in MOD and EXT was also observed when stimulated by ConA and LPS similarly to SED. Acute exercise promoted decreased glutamine plasma concentration and changes in glutamine metabolism that did not impair lymphocyte proliferation in exhaustive trained rats.     

Glucose ingestion before and during exercise does not enhance performance of daily repeated endurance exercise

The effect of glucose (Glc) ingestion before and during daily, repeated, prolonged exercise on metabolism and performance was tested. Seven young, healthy males performed cycling exercise in two series, with 1 month interval. Each exercise series consisted of 1 h/day on 3 successive days. On the 3rd day, exercise was continued until exhaustion. The intensity was 73.4 (7.7) % [mean (SD)] of maximal oxygen uptake ( ). Glucose (Glc) or placebo (P) drink was ingested 15 min before the start, and at 15 and 45 min of each daily exercise. The total amount of Glc ingested was 43.1 (4.2) g. During exercise, blood Glc concentrations were significantly higher (P<0.05) when Glc was ingested than when P was ingested [Glc 5.14 (0.32) and P 4.12 (4.17) mmol · 1^–1 at exhaustion]. However, Glc ingestion did not improve performance time to exhaustion [Glc 92.05 (29.55) and P 98.07 (27.33) min]. Free fatty acid concentrations were significantly lower when Glc was ingested than when P was ingested [Glc 0.63 (0.21) and P 1.39 (0.46) mmol · l^–1 at exhaustion]. There were no significant differences in exercise heart rate, , respiratory exchange ratio, blood lactate concentrations or rating of perceived exertion between the conditions nor were there any significant differences in these parameters on different days of exercise. It seems that ingestion of small amounts of Glc does not increase the metabolism of carbohydrate or improve the performance of intensive endurance exercise of poorly trained subjects, even when the exercise is repeated daily.     

抗阻运动对高脂饮食诱导的肥胖大鼠脂肪组织自噬和炎症因子的影响

为探讨运动对肥胖患者自噬活性和内脏脂肪组织炎症反应的影响,本研究将60只肥胖小鼠随机分为高脂饮食组(B)、正常饮食组(C)、正常饮食加耐力运动干预组(D)、正常饮食加耐力运动干预组(E)。D组和E组分别进行10周的耐力和抗阻运动,然后用RT-PCR检测自噬、炎症的基因和蛋白表达。结果显示,三个干预组的Lee指数和BFI均显著降低,2个运动组的Lee指数和BFI均显著降低,但差异无显著性;D组和E组Beclin 1表达较C组显著降低,p62表达明显升高;与C组相比,D组p62显著升高,E组无明显升高;与D组相比,E组Beclin 1基因表达增加,p62蛋白表达降低;与C组相比,D组和E组IL-6和IL-0蛋白表达均显著升高;10周不同运动干预对大鼠减脂效果无差异。运动后内脏脂肪组织的自噬活性受到抑制,尤其是无氧运动;肥胖患者运动干预前后内脏脂肪组织自噬和炎症的变化趋势一致,其中IL-10的变化最为明显。     

Non-invasive assessment of animal exercise stress: real-time PCR of GLUT4, COX2, SOD1 and HSP70 in avalanche military dog saliva

Exercise has been shown to increase mRNA expression of a growing number of genes. The aim of this study was to assess if mRNA expression of the metabolism- and oxidative stress-related genes GLUT4 (glucose transporter 4), COX2 (cyclooxygenase 2), SOD1 (superoxide dismutase 1) and HSP70 (heat shock protein 70) in saliva changes following acute exercise stress in dogs. For this purpose, 12 avalanche dogs of the Italian Military Force Guardia di Finanza were monitored during simulation of a search for a buried person in an artificial avalanche area. Rectal temperature (RT) and saliva samples were collected the day before the trial (T0), immediately after the descent from a helicopter at the onset of a simulated avalanche search and rescue operation (T1), after the discovery of the buried person (T2) and 2 h later (T3). Expressions of GLUT4, SOD1, COX2 and HSP70 were measured by real-time PCR. The simulated avalanche search and rescue operation was shown to exert a significant effect on RT, as well as on the expression of all metabolism- and oxidative stress-related genes investigated, which peaked at T2. The observed expression patterns indicate an acute exercise stress-induced upregulation, as confirmed by the reductions in expression at T3. Moreover, our findings indicate that saliva is useful for assessing metabolism- and oxidative stress-related genes without the need for restraint, which could affect working dog performance.     

Dynamic alteration of plasma levels of betatrophin in younger female onset obesity post acute moderate-intensity exercise training

Obesity is a global metabolic disease anchored by a lack of physical activity lipid disturbances. Hitherto, betatrophin is a potential liver-derived hormone that regulates lipid metabolism. A total of 26 selected onset obese individuals (BMI range ± 28–31) were enrolled in this study and given moderate-intensity exercise. Importantly, our data show that acute moderate-intensity interval exercise (MIIE) and acute moderate-intensity continue to exercise (MICE) for 40 min significantly decrease the plasma level of full-length betatrophin respectively (174.18 ± 48.19 ng/mL; 182.31 ± 52.69 ng/mL), compared to the placebo (283.97 ± 32.23 ng/mL) post 10 min and 6 h exercise treatment (p ≤ 0.05). The plasma level of betatrophin was significantly and negatively correlated with BMI (r = ? 0.412, p = 0.037), fasting blood glucose (r = ? 0.390, p = 0.049), and positively correlated with VO_2max (r = 0.456, p = 0.019). In addition, the linear and ordinal logistic regression analysis shows that betatrophin, is a potential predictor for BMI [estimate value = 0.995, p = 0.037 and OR (95 % CI) = 0.992 (0.0984–1.00), p = 0,048]. In summary, our data demonstrate that the circulating levels of betatrophin were decreased after acute moderate-intensity exercise training.     

大鼠一次性力竭跑台运动模型的建立及动态评价

目的跑台急性运动疲劳动物模型的建立及评价。方法选取清洁级雄性Wistar大鼠24只(8周龄)作为实验对象。采用多级递增负荷跑台运动方案(跑台坡度为0°,负荷分为三级)建立一次性力竭跑台运动动物模型。尾静脉取血,分别测定大鼠在安静、运动30 min、运动90 min、力竭、恢复30 min、恢复90 min各时间点外周血葡萄糖(GLU)、乳酸(LD)、尿素(BU)、丙二醛(MDA)浓度和肌酸激酶(CK)、超氧化物歧化酶(SOD)活性。结果一次性力竭运动过程中大鼠行为能力和运动能力、血液代谢产物及能量物质呈现阶段性的动态变化。外周血LD、BU、MDA浓度及CK活性均较安静时显著性增高(P<0.01,P<0.05);GLU浓度、SOD活性较安静时显著降低(P<0.01,P<0.05)。各指标的变化特征说明大鼠已达到运动疲劳状态。结论建立了大鼠一次性力竭跑台运动模型,并客观动态评价了大鼠在运动疲劳产生、发展、恢复等不同阶段各指标的变化特点及规律。该模型可用于后续运动疲劳机制的相关研究。     

橘皮素对高强度运动诱发的人体皮质醇应激反应的影响*

目的: 探讨4周橘皮素补充对高强度抗阻运动诱发的皮质醇应激反应的影响。方法: 将24名短跑运动员进行配对,随机分为试验组和对照组。试验组每天补充橘皮素补剂(含橘皮素200 mg),对照组每天补充安慰剂,为期4周。两组运动员均在干预前一日和干预后次日进行抗阻运动激发试验(推举、深蹲、卧推和硬拉,每个动作×4组×10RM)。采集受试者在运动激发试验前即刻(PRE)、试验后即刻(P0)以及第10(P10)、20(P20)和30(P30)分钟时的血液样本,测量血清皮质醇、促肾上腺皮质激素(ACTH)、超氧化物歧化酶(SOD)、白细胞计数(WBC)和血糖,以及PRE和P0时的血乳酸值。结果: 与干预前同期比较,补充橘皮素4周后,试验组在激发试验前PRE的血清皮质醇水平(P=0.017)、激发试验后P10的血清皮质醇水平(P=0.010)、激发试验后P20和激发试验后P30的血清皮质醇水平均显著降低(P＜0.05或 P＜0.01),试验组在激发试验前PRE的WBC、激发试验后P10的ACTH(P=0.037)和激发试验后P30的WBC、ACTH均显著降低(P＜0.05);与对照组比较,试验组在激发试验前PRE和激发试验后P10的血清皮质醇水平显著降低(P＜0.05),激发试验后P30的ACTH和WBC水平显著降低(P＜0.05,P＜0.01)、SOD活性水平显著升高(P＜0.05)。结论: 橘皮素能有效缓解高强度运动诱发的人体皮质醇应激反应,抑制皮质醇过度分泌,提升人体抗氧化能力,加速体内炎症消除,促进身体机能恢复。