常氧、低氧训练条件下肌肉蛋白表达及肌张力的变化

背景：环境因素以及运动水平均可显著引起肌纤维结构的变化。目的：观察常氧、低氧训练条件下大鼠腓肠肌肌球蛋白、肌动蛋白的表达及肌张力的变化特征。方法：将SD大鼠随机分为常氧对照组（氧体积分数20%,不进行任何处理）、常氧训练2,4,6周组、低氧训练2,4,6周组、低氧对照组（氧体积分数12.7%,不进行训练）。结果与结论：无论在常氧还是低氧环境下,运动训练后大鼠腓肠肌质量、腓肠肌肌纤维截面积均明显增加（P〈0.05,P〈0.01）;运动训练6周后大鼠腓肠肌等长收缩最大张力显著增加（P〈0.01）;经运动训练后大鼠腓肠肌总MHC及α-actin随着训练时间的延长逐步升高,并且低氧训练组升高幅度高于常氧训练组。说明低氧训练可以更有效促进骨骼肌肌球蛋白、肌动蛋白的表达,增强肌张力,强化Ⅰ型肌纤维,并且训练时间越长,效果越显著,表明低氧训练是一种有效的运动训练途径。     

腓肠肌肌球蛋白收缩功能在有氧训练后的变化

背景:已有实验证实长期耐力训练能导致肌纤维及其肌球蛋白重链异形体由快型向慢型转变,但对于运动训练中肌球蛋白重链异形体mRNA的变化仍有待进一步的实验观察与验证。目的:观察跑台训练对雄性SD大鼠腓肠肌肌球蛋白收缩功能的影响。设计:随机对照动物实验。单位:西安交通大学医学实验中心。材料:选用40只生后7周雄性SD大鼠,体质量(230±16)g,所有动物实验前均未进行过跑台运动。试剂:一抗为鼠源性抗骨骼肌肌动蛋白及快缩型肌球蛋白重链(MHCⅡ)单克隆抗体,ABCam产品。二抗为偶合碱性磷酸酶的抗鼠IgG,SIGMA产品。方法:实验于2005-03/10在西安交通大学医学实验中心完成。随机摸球法将大鼠分为对照组(n=10)和训练组(n=30)。训练组大鼠进行连续4～6周强度约为75%VO2max(18.5～24m/min,坡度为0°)的跑台训练,50min/次,2次/d。对照组自由活动,不给予任何干预措施。训练至4,5,6周,分别取10只大鼠,采用反转录聚合酶链式反应腓肠肌肌球蛋白重链mRNA含量,以免疫组化方法检测肌球蛋白肌纤维的改变情况及横截面积的大小,大鼠麻醉后游离腓肠肌,采用张力传感器及电刺激器给予方波脉冲刺激,逐步拉伸腓肠肌至等长收缩张力为最大时的肌肉初长Lmax位置,平衡10min,记录肌肉长度与张力。取右侧腓肠肌称量湿质量,计算其与体质量之比。肌肉质量与体质量之比按下式计算:肌肉质量(mg)/体质量(g)×100%。主要观察指标:①腓肠肌肌球蛋白重链mRNA含量。②肌球蛋白肌纤维的改变情况及横截面积的大小。③大鼠体质量与腓肠肌质量的变化。④腓肠肌等长收缩最大张力。结果:纳入大鼠40只全部进入结果分析。①腓肠肌肌球蛋白重链mRNA含量:经过4周耐力训练,训练组肌球蛋白总肌球蛋白重链表达是对照组的105%(P<0.01),肌球蛋白重链Ⅱa表达量高于对照组(1.27±0.08,1.17±0.06,P<0.05),肌球蛋白重链ⅡxmRNA表达量高于对照组(1.29±0.04,1.19±0.05,P<0.01)。②肌球蛋白肌纤维的改变情况及横截面积的大小:经过4～6周的有氧训练后,大鼠肌球蛋白重链主要以Ⅱ型慢缩型肌纤维表达为主,而Ⅰ型快缩型肌纤维表达较少。对照组大鼠腓肠肌Ⅰ、Ⅱ型肌纤维横截面积分别为(1958.0±30.5),(1656.1±35.3)mm2。而训练组4周后Ⅰ、Ⅱ型肌纤维横截面积较对照组分别增加24.5%与22.1%(P<0.01);训练组5周后分别增加26.4%与51.5%(P<0.01),训练组训练6周后分别增加33.2%与48.9%(P<0.01)。③大鼠体质量与腓肠肌质量的变化:训练组大鼠训练4,5,6周腓肠肌湿质量分别为(135.6±3.1),(139.2±5.1),(148.4±6.2)mg,高于对照组[(103.2±3.4),(87.5±2.9),(68.3±3.3)mg,P<0.01]。训练组大鼠训练4,5,6周腓肠肌相对湿质量分别为(0.55±0.01),(0.56±0.02),(0.59±0.03),高于对照组[(0.43±0.02),(0.37±0.04),(0.29±0.05),P<0.05～0.01]。④腓肠肌等长收缩最大张力:方波脉冲刺激后6周训练组等长收缩最大张力较对照组显著增加(P<0.01)。结论:短期耐力训练后,肌球蛋白重链中的两种慢型肌球蛋白重链异形体-肌球蛋白重链Ⅱx、肌球蛋白重链Ⅱb基因表达增加,肌纤维横截面积增加,等长收缩最大张力增加,表明有氧训练对提高肌球蛋白收缩功能有促进作用。     

有氧训练大鼠腓肠肌组织微小RNA-133a和肌细胞增强因子2的表达

背景:研究表明微小RNA-133a、肌细胞增强因子2和成肌分化抗原可调解骨骼肌的分化与重塑。目的:观察有氧训练对腓肠肌微小RNA-133a、肌细胞增强因子2和成肌分化抗原表达的影响。方法:将SD大鼠随机分为对照组和有氧训练组,有氧训练组采用大鼠跑台运动模型,而对照组不进行运动训练。训练4,6周后采集各组大鼠腓肠肌组织,并称取腓肠肌的质量,实时定量PCR检测骨骼肌中肌球蛋白、微小RNA-133a、肌细胞增强因子2与成肌分化抗原mRNA的表达,并采用免疫组织化学的方法检测腓肠肌Ⅱ型肌纤截面积的改变。结果与结论:训练4,6周,有氧训练组大鼠腓肠肌的相对质量以及肌球蛋白重链-Ⅱa的表达水平较对照组显著增加(P<0.05或P<0.01),Ⅱ型肌纤维横截面积即显著增大(P<0.05),其微小RNA-133a和肌细胞增强因子2mRNA的表达较对照组显著升高(P<0.05,P<0.01),而成肌分化抗原mRNA的表达在各组间差异均无显著性意义。证实,有氧训练可上调大鼠腓肠肌组织微小RNA-133a、肌细胞增强因子2mRNA的表达。     

低氧训练与低氧大鼠心肌细胞凋亡及凋亡因子的表达

背景：低氧训练时,机体既要承受运动负荷,同时处于外界的低氧环境,此时,心组织将如何适应其变化？其机制研究国内外较少。目的：观察低氧与低氧训练对大鼠心肌细胞凋亡及Bax及Bcl-2表达的影响。方法：SD大鼠共60只随机分为6组,常氧组、低氧8h组、低氧12h组、常氧训练组、低氧8h训练组和低氧12h训练组,每组10只。后3组大鼠每天在坡度为0的动物跑台上以25m／min的速度训练1h。训练完后,将低氧8h组、低氧8h训练组和低氧12h组、低氧12h训练组放入氧体积分数为12．5％（相当于海拔4000m）的低氧舱内8h和12h。实验期为4周,5d／周。最后1次实验结束后24h,大鼠均实施速眠新II腹腔麻醉后取材,采用苏木精-伊红染色、原位末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记法及蛋白免疫组织化学法检测各组大鼠心肌细胞凋亡和Bcl-2、Bax蛋白表达。结果与结论：①与常氧组相比,低氧12h组、常氧训练组、低氧训练组心肌细胞凋亡指数均显著增加（P〈0．05）;低氧12h训练组心肌细胞凋亡指数显著多于常氧训练组和低氧8h训练组（P〈0．05）。②与常氧组比较,其他各组Bcl-2、Bax、Bcl-2／Bax均显著性增高（P〈0．05）：常氧训练组Bcl-2、Bax、Bcl-2／Bax表达显著高于低氧8h组,显著低于低氧12h训练组（P〈0．05）;低氧12h训练组Bcl-2、Bax、Bcl-2／Bax表达比低氧12h组、低氧8h训练组显著增加（P〈0．05）。提示低氧、低氧训练可诱导大鼠心肌细胞Bcl-2、Bax蛋白表达,运动时低氧刺激与细胞凋亡率、凋亡指数及病理损伤有关,其中以低氧12h后运动训练组最明显,心肌细胞的凋亡调控与Bcl-2和Bax相关。     

低氧及跑台运动对大鼠左心室肌线粒体超微结构的影响

目的:观察低氧及低氧复合跑台运动后大鼠左心室肌细胞内线粒体超微结构的变化,探讨低氧及运动训练对心肌线粒体的影响。方法:成年雄性SD大鼠40只,随机分为4组:常氧对照组、常氧运动组、低氧对照组及低氧运动组。用MPA-心功能分析系统记录血压和心率,用透射电镜观察各组大鼠心肌线粒体的超微结构。结果:常氧对照组:线粒体结构完整,平行排列。常氧运动组:线粒体数量增加,体积增大,轻度水肿。低氧对照组:线粒体排列紊乱,挤压变形,嵴断裂,外膜增厚。低氧运动组:线粒体平行排列,基质增多,部分线粒体结构不清,肌膜尚清晰。结论:低氧导致左心室肌线粒体结构严重破坏,运动使线粒体数量增加,体积增大。适度的运动训练可明显改善低氧对大鼠心肌线粒体的损伤,对心脏有一定的保护作用。     

急性低氧及低氧复合运动对骨骼肌及代谢酶活性的影响

目的:观察急性低氧(3d)及低氧复合运动对大鼠腓肠肌肌纤维形态以及血清肌型肌酸激酶同工酶(CK-MM)和乳酸脱氢酶同工酶(LDH5)活性的影响,探讨运动在骨骼肌急性低氧适应中的意义。方法:分别建立大鼠急性低氧及低氧复合运动模型,将动物随机抽签法分为单纯低氧组(A组),低氧适应性训练组(B组),常氧对照组(C组),观察腓肠肌肌纤维的形态变化,测定血清CK-MM和LDH5活性的变化。结果:单纯急性低氧条件下,大鼠腓肠肌肌纤维轻度萎缩,血清酶学改变明显,而低氧复合运动则无显著变化。A组CK-MM为(690.5±120.3)IU/L,LDH5为(8.9±2.2)IU/L,B组CK-MM为(282.7±60.7)IU/L,LDH5为(5.3±1.5)IU/L,C组CK-MM为(278.7±20.3)IU/L,LDH5为(4.8±1.2)IU/L,A组与C组比较,t=10.7,P<0.001,B组与C组比较t=0.02,P>0.05。结论:急性低氧条件下适当运动可以提高骨骼肌的低氧适应能力,起到保护骨骼肌的作用。     

低氧和长时间游泳运动对小鼠骨骼肌低氧诱导因子1α和糖代谢酶活性的影响

目的:模拟“高住低训”条件,观察低氧和长时间游泳运动对小鼠骨骼肌低氧诱导因子1α及乳酸脱氢酶、琥珀酸脱氢酶活性的影响。方法:实验于2004-06/08在华东师范大学生物化学实验室完成。选择雄性成年昆明小鼠18只,适应性训练1周后,按随机数字表法分为3组,即低氧对照组、低氧训练组和常氧对照组,每组6只。制备模拟低氧设备,低氧对照组进行8周的低氧适应,8h/次,5次/周,氧浓度控制在156～161mL/L。低氧训练组进行8周的低氧适应和常氧游泳训练,每次先进行8h的低氧适应后再进行1h的常氧游泳训练,5次/周。常氧对照组按常规饲养。8周后,3组小鼠均在一次性力竭运动后立即麻醉断头处死,取股外侧肌,分为两块,一块测定乳酸脱氢酶和琥珀酸脱氢酶活性;另一块测定细胞中低氧诱导因子1α蛋白含量(免疫组织化学法)。结果:饲养过程中常氧对照组脱失1只,进入结果分析低氧对照组、低氧训练组和常氧对照组分别为6,6,5只小鼠。①常氧对照组小鼠骨骼肌细胞内低氧诱导因子1α蛋白几乎无表达,而低氧训练组和低氧对照组小鼠骨骼肌细胞内低氧诱导因子1α蛋白含量较高,两组均有6个以上目标蛋白。②低氧对照组、低氧训练组小鼠骨骼肌乳酸脱氢酶和琥珀酸脱氢酶的活性均有显著高于常氧对照组[(128.49±11.83,145.37±14.33,93.65±15.32)μkat/g;(223.21±51.01,252.05±48.18,99.02±32.67)nkat/g(P<0.01)],其中低氧训练组显著高于低氧对照组(P<0.01)。结论:在模拟“高住低训”条件下,低氧加长时间大负荷运动能够促进低氧诱导因子1α蛋白的表达,提高骨骼肌糖的有氧代谢酶的活性,有利于增强机体运动功能。而且骨骼肌低氧诱导因子1α蛋白含量与乳酸脱氢酶、琥珀酸脱氢酶活性可能存在着一定的关系。     

低氧复合常氧训练增强大鼠腓肠肌琥珀酸脱氢酶的活性

背景低氧训练对骨骼肌能量代谢的影响是运动医学的研究热点.而目前有关低氧训练改善骨骼肌有氧氧化、无氧代谢能力的证据并不充分.目的探讨低氧复合常氧训练对骨骼肌有氧和糖酵解能力的影响.设计随机实验观察.单位北京体育大学运动人体科学学院.材料实验于2003-03/07在河北体育科学研究所完成.选择7周龄健康雄性SD大鼠96只,随机分为4大组对照组、低氧对照组、低氧复合常氧训练组和常氧训练组.根据实验组4,7,28 d取样时间的不同,将每大组随机分成3小组,每组8只.方法建立模拟海拔4 000米中等强度低氧复合常氧训练4周的动物模型(跑台坡度10%,跑速20m/min,1次/d,1h/次,5次/周,共4周),剪取腓肠肌肌腹红白混合处约0.5 g,经处理后待测.采用紫外分光光度法测定10%腓肠肌匀浆液中琥珀酸脱氢酶活力.腓肠肌乳酸脱氢酶活性采用半自动生化分析仪内设的"速率法",测定0.5%腓肠肌匀浆液中乳酸脱氢酶活力.总蛋白浓度采用半自动生化分析仪内设的"终点法"-双缩脲法.主要观察指标在不同观察时间腓肠肌琥珀酸脱氢酶和乳酸脱氢酶活性的变化.结果实验过程中无动物死亡,全部进入结果分析.①单纯低氧刺激可以引起琥珀酸脱氢酶活性升高,但随时间推移呈逐渐降低趋势;而低氧复合常氧训练使琥珀酸脱氢酶活性在4～28 d的各观察期都显著升高,且与单纯低氧间呈剪刀式变化.其中在第28天观察时比对照组高约2倍.②单纯低氧刺激、单纯常氧训练都使乳酸脱氢酶活性降低;而低氧复合常氧训练的乳酸脱氢酶活性基本稳定在对照水平.结论模拟海拔4 000m,中等强度的低氧复合常氧训练,4周时间内即可提高腓肠肌琥珀酸脱氢酶活性.预示低氧复合常氧训练能提高骨骼肌有氧代谢潜能.同样训练环境和运动负荷,未能提高腓肠肌乳酸脱氢酶活性,即4周的低氧复合常氧训练未必能改善骨骼肌糖酵解供能能力.     

低氧运动对SD大鼠白细胞及其分类计数的影响

目的:观察低氧及运动对大鼠白细胞及其分类计数的影响。方法:实验于2005-03/05在广州体育学院运动生化省重点实验室进行。随机选择34只喜好运动,能在跑台上自觉跑步的SD大鼠数字表法随机分为常氧安静组、常氧运动组、低氧安静组、低氧运动组4组,常氧运动组在常氧状态下(氧的体积分数是0.209)进行25m/min的跑台训练,低氧运动组大鼠常压低氧环境(氧的体积分数是0.154,相当于2500m高度)下进行20m/min的跑台训练,训练时间均为1h/d,6d/周,持续4周。常氧安静组和低氧安静组分别在常氧和低氧环境中4周,不运动。4周后大鼠禁食12h,腹主动脉取血,采用德国Bayer公司的ADVIA120全自动血球分析仪测定血液中白细胞总数、中性粒细胞、淋巴细胞、单核细胞、嗜酸细胞、嗜碱细胞计数。结果:34只大鼠全部进入结果分析。①白细胞总数和淋巴细胞各组间比较差异不显著(P>0.05)。②中性粒细胞计数:低氧安静组和低氧运动组低于常氧运动组[(0.15±0.05)×103,(0.14±0.10)×103,(0.35±0.39)×103L-1,P<0.05,0.01]。③单核细胞计数:低氧安静组和低氧运动组低于常氧安静组[(0.48±0.32)×103,(0.53±0.30)×103,(1.08±0.53)×103L-1,P<0.05,0.01]。④嗜酸细胞计数:常氧运动组、低氧安静组和低氧运动组低于常氧安静组[(0.008±0.009)×103,(0.007±0.008)×103,(0.013±0.009)×103,(0.047±0.029)×103L-1,P<0.01]。⑤嗜碱细胞计数:低氧安静组和低氧运动组低于常氧运动组[(0.007±0.005)×103,(0.006±0.005)×103,(0.018±0.015)×103L-1,P<0.05]。结论:长期的低氧适应能显著性降低运动大鼠中性粒细胞反应性,并显著性降低安静大鼠的单核细胞及嗜酸细胞数,造成机体部分非特异性免疫力有所下降。     

低氧复合常氧训练增强大鼠腓肠肌琥珀酸脱氢酶的活性

背景：低氧训练对骨骼肌能量代谢的影响是运动医学的研究热点．而目前有关低氧训练改善骨骼肌有氧氧化、无氧代谢能力的证据并不充分。目的：探讨低氧复合常氧训练对骨骼肌有氧和糖酵解能力的影响，设计：随机实验观察。单位：北京体育大学运动人体科学学院。材料：实验于2003-03／07在河北体育科学研究所完成。选择7周龄健康雄性SD大鼠96只，随机分为4大组：对照组、低氧对照组、低氧复合常氧训练组和常氧训练组。根据实验组4，7，28d取样时间的不同，将每大组随机分成3小组，每组8只。方法：建立模拟海拔4000米中等强度低氧复合常氧训练4周的动物模型（跑台坡度10％，跑速20m／min，1次／d，1h／次，5次／周，共4周），剪取腓肠肌肌腹红白混合处约0．5g，经处理后待测。采用紫外分光光度法测定10％腓肠肌匀浆液中琥珀酸脱氢酶活力．腓肠肌乳酸脱氢酶活性采用半自动生化分析仪内设的“速率法”，测定0．5％腓肠肌匀浆液中乳酸脱氢酶活力。总蛋白浓度采用半自动生化分析仪内设的“终点法”-双缩脲法。主要观察指标：在不同观察时间腓肠肌琥珀酸脱氢酶和乳酸脱氢酶活性的变化。结果：实验过程中无动物死亡，全部进入结果分析。①单纯低氧刺激可以引起琥珀酸脱氢酶活性升高，但随时间推移呈逐渐降低趋势；而低氧复合常氧训练使琥珀酸脱氢酶活性在4～28d的各观察期都显著升高，且与单纯低氧间呈剪刀式变化。其中在第28犬观察时比对照组高约2倍。②单纯低氧刺激、单纯常氧训练都使乳酸脱氢酶活性降低；而低氧复合常氧训练的乳酸脱氢酶活性基本稳定在对照水平。结论：模拟海拔4000m，中等强度的低氧复合常氧训练，4周时间内即可提高腓肠肌琥珀酸脱氢酶活性。预示低氧复合常氧训练能提高骨骼肌有氧代谢潜能。同样训练环境和运动负荷，未能提高腓肠肌乳酸脱氢酶活性，即4周的低氧复合常氧训练未必能改善骨骼肌糖酵解供能能力。     

低氧训练大鼠骨骼肌组织低氧诱导因子1对血管新生的影响

背景:低氧诱导因子1是一种在氧平衡调节中起关键作用的转录因子,与机体的耐缺氧能力密切相关。目的:观察低氧训练大鼠骨骼肌组织中低氧诱导因子1和血管内皮CD34的蛋白表达,探讨低氧诱导因子1在促进骨骼肌组织血管形成中的作用。方法:将健康雄性SD大鼠60只,随机分为6组:常氧对照组、低氧不运动组、常氧训练组、低住高练组、高住低练组和高住高练低练组。运动组采用10周递增负荷跑台运动训练,每周训练6d,运动量由第1周的速度为15m/min、持续时间为25min递增至第10周速度为28m/min、持续时间为50min,低练组每周二、四、六在相当于海拔1500m的低氧环境中训练,并且在低氧环境中居住,低氧程度由第1周相当于海拔1800m递增至第10周相当于海拔3600m。结果与结论:低氧状态下,低氧诱导因子1有大量的蛋白表达,低氧复合运动表达更多,而CD34蛋白表达只发生在常氧运动组和低氧训练组。提示低氧诱导因子1是促进骨骼肌组织血管新生的一种重要因子,但须结合运动才能产生积极的作用。     

Effects of resistance training under hypoxic conditions on muscle hypertrophy and strength

It has been reported that exercise under hypoxic conditions elevates acute growth hormone secretion after exercise compared with that under normoxic conditions. This study examined the influence of resistance training under moderate hypoxic conditions on muscle thickness, strength and hormonal responses. Thirteen healthy men were assigned into two groups matched for physical fitness level and then randomized into two groups that performed exercise under normoxic (FiO₂ = 20·9%) or hypoxic (FiO₂ = 12·7%) conditions. Three sets of elbow extensions with unilateral arm were performed to exhaustion at a workload of a 10 repetition maximum with 1‐minute intervals for 3 days per week for 8 weeks. The thickness of the biceps and triceps brachii was determined using B‐mode ultrasound before and after training. Blood sampling was carried out before and after exercise, as well as during the first and last training sessions. Increase in the thickness of the triceps brachii in trained arm was significantly greater in the hypoxic group than in the normoxic group. The 10 repetition maximum was significantly increased not only in the trained arm but also in the untrained arm in both groups. Serum growth hormone concentrations after exercise were significantly higher in the hypoxic group than in the normoxic group on both the first and last training sessions. These findings suggest that hypoxic resistance training elicits more muscle hypertrophy associated with a higher growth hormone secretion, but that the greater muscle hypertrophy did not necessarily contribute a greater gain of muscle strength.     

Intermittent hypoxic training: implications for lipid peroxidation induced by acute normoxic exercise in active men.

Oxidant generation during regular physical exercise training may influence the adaptive responses that have been shown to confer protection against oxidative stress induced by subsequent acute exercise. To examine this, we randomly assigned 32 males to either a normoxic (n=14) or a hypoxic (n=18) group. During the acute phase, subjects in the hypoxic group performed two maximal cycling tests in a randomized double-blind fashion: one under conditions of normoxia and the other under hypoxic conditions (inspired fraction of O(2)=0.21 and 0.16 respectively). During the intermittent phase, the normoxic and hypoxic groups each trained for 4 weeks at the same relative exercise intensity, under conditions of normoxia and hypoxia respectively. During acute exercise under hypoxic conditions, the venous concentrations of lipid hydroperoxides and malondialdehyde were increased, despite a comparatively lower maximal oxygen uptake (VO(2max)) (P<0.05 compared with normoxia). The increases in lipid hydroperoxides and malondialdehyde were correlated with the exercise-induced decrease in arterial haemoglobin oxygen saturation (r=-0.61 and r=-0.50 respectively; P<0.05), but not with VO(2max). Intermittent hypoxic training attenuated the increases in lipid hydroperoxides and malondialdehyde induced by acute normoxic exercise more effectively than did normoxic training, due to a selective mobilization of alpha-tocopherol (P<0.05). The latter was related to enhanced exercise-induced mobilization/oxidation of blood lipids due to a selective increase in VO(2max) (P<0.05 compared with normoxic group). We conclude that lipid peroxidation induced by acute exercise (1) increases during hypoxia; (2) is not regulated exclusively by a mass action effect of VO(2); and (3) is selectively attenuated by regular hypoxic training. Oxidative stress may thus be considered as a biological prerequisite for adaptation to physical stress in humans.     

Resolution of hypoxic changes in the heart and pulmonary arterioles of rats during intermittent correction of hypoxia.

1. Rats kept in a hypoxic chamber (10% O2) for 3 or more weeks developed right ventricular hypertrophy, muscularization of pulmonary arterioles and polycythaemia. These changes resemble those found in human hypoxic disease and, in particular, in patients dying from chronic airways obstruction. 2. Resolution of these changes was studied in a normal environment and in an intermittently normal, intermittently hypoxic environment. The latter regimen modelled the situation of patients with cor pulmonale receiving long-term intermittent oxygen therapy. 3. In a normal environment right ventricular hypertrophy and polycythaemia were resolved in 6 weeks but vessel changes were not resolved in 12 weeks. 4. In the intermittently normoxic environment (40 or 80 h in air per week) there was some resolution of right ventricular hypertrophy in 6 weeks but no significant reduction in vessel thickening or in polycythaemia in 12 weeks.     

Hypoxic exercise training promotes antitumour cytotoxicity of natural killer cells in young men

The cytotoxic functions of NKs (natural killer cells) are critical in enabling the immune system to cope efficiently with malignancy. In the present study, we compared how various exercise regimens without/with hypoxia influence phenotypic characteristics of NK subsets and cytotoxicity of NKs to NPCs (nasopharyngeal carcinoma cells). A total of 60 sedentary males were randomly divided into five groups. Each group (n=12) underwent one of five regimens: normoxic (21% O(2)) control (N-C), hypoxic (15% O(2)) control (H-C), normoxic exercise (50% maximal work rate under 21% O(2); N-E), hypoxic relative exercise (50% maximal heart rate reserve under 15% O2; H-RE) or hypoxic absolute exercise (50% maximal work rate under 15% O(2); H-AE) for 30 min/day, 5 days/week for 4 weeks. The results showed that hypoxic exercise regimens increased pulmonary ventilation and tissue oxygen utilization. Moreover, the H-RE regimen resulted in enhanced aerobic fitness at a less intensive training workload in the H-AE regimen. Before each regimen, strenuous exercise elevated NK perforin/granzyme B content and promoted cytotoxicity of NKs to NPCs. However, the percentage of NKs expressing homing (CD11a)/terminally differentiated (CD57)/inhibitory [KLRG1 (killer cell lectin-like receptor G1)] molecules that entered the bloodstream from peripheral tissues increased following this exercise. After 4 weeks, both the H-AE and H-RE regimens produced an up-regulated expression of memory (CD45RO)/activating (NKG2D) molecules and was accompanied by a decrease in CD57/KLRG1 levels on NKs at rest and after strenuous exercise. Furthermore, the two regimens increased resting and exercise NK perforin/granzyme B content and NK-induced phosphatidylserine exposure of NPCs. In contrast, no significant change in the phenotypic characteristics of blood NK subsets or NK-induced NPC apoptosis was observed in the N-C, H-C and N-E regimens. Therefore we conclude that 15% O(2) exercise training reduces terminally differentiated NK subsets and up-regulates the expression of activating molecules and cytotoxic granule proteins in NKs, thereby enhancing the capacity of anti-NPC cytotoxicity by NKs. These findings could help to determine effective hypoxic exercise regimens for improving individual aerobic capacity and simultaneously promoting the natural cytotoxicity of NKs.     

Additive and synergistic effects of bFGF and hypoxia on leporine meniscus cell‐seeded PLLA scaffolds

Injuries to avascular regions of menisci do not heal and result in significant discomfort to patients. Current treatments, such as partial meniscectomy, alleviate these symptoms in the short term but lead to premature osteoarthritis as a result of compromised stability and changes in knee biomechanics. Thus, tissue engineering of the meniscus may provide an alternative treatment modality to overcome this problem. In this experiment, a scaffold‐based tissue‐engineering approach was utilized to regenerate the meniscus. Meniscus cells were cultured on poly‐L ‐lactic acid scaffolds in normoxic (～21% oxygen) or hypoxic (～2% oxygen) conditions in the presence or absence of the growth factor, basic fibroblast growth factor (bFGF). At t = 4 weeks, histological sections of constructs showed presence of collagen and glycosaminoglycan (GAG) in all groups. Immunohistochemical staining showed the presence of collagen I in all groups and collagen II in groups cultured under hypoxic conditions. bFGF in the culture medium significantly increased cell number/construct by 25%, regardless of culture conditions. For GAG/construct, synergistic increases were observed in constructs cultured in hypoxic conditions and bFGF (two‐fold) when compared to constructs cultured in normoxic conditions. Compressive tests showed synergistic increases in the relaxation modulus and coefficient of viscosity and additive increases in the instantaneous modulus for constructs cultured under hypoxic conditions and bFGF, when compared to constructs cultured under normoxic conditions. Overall, these results demonstrate that bFGF and hypoxia can significantly enhance the ability of meniscus cells to produce GAGs and improve the compressive properties of tissue‐engineered meniscus constructs in vitro. Copyright © 2009 John Wiley & Sons, Ltd.     

不同强度的耐力运动对糖尿病大鼠骨骼肌 GLUT4 mRNA表达的影响

目的探讨不同强度的耐力运动对糖尿病大鼠骨骼肌GLUT4 mRNA表达的影响.方法雄性SD大鼠,其中36只大鼠经尾静脉注射链脲霉素,建立糖尿病模型.然后随机分为低强度运动组(EL)、高强度运动组(EH)、低强度运动加胰岛素治疗组(LI)、高强度运动加胰岛素治疗组(HI)、胰岛素治疗非运动组(DI)和非胰岛素治疗非运动组(DM).6只SD大鼠为非运动正常血糖组(CN).耐力训练采用活动平板,胰岛素采用皮下注射,共8周.运用RT-PCR法测定骨骼肌GLUT4 mRNA.结果DM组骨骼肌GLUT4 mRNA表达水平显著低于其它各组(P＜0.05).LI组骨骼肌GLUT4 mRNA表达水平明显增高接近CN组,并且显著高于DI组.DI组GLUT4 mRNA含量与EL、EH、HI各组相当,差异无显著性意义.结论运动可以促进GLUT4 mRNA的表达,而运动强度对GLUT4 mRNA表达量无显著影响;低强度运动加胰岛素所具有最佳的GLUT4 mRNA表达水平是其它单独干预措施所无法替代的.