止血带缺血预处理对大鼠肢体缺血再灌注损伤的保护作用——电生理学研究

目的 :研究止血带缺血预处理对大鼠肢体骨骼肌、外周神经缺血再灌注损伤的保护作用。方法 :选择健康SD大鼠 5 0只 ,随机分成实验组和对照组。用特制气囊止血带制成大鼠后肢缺血再灌注损伤模型 ,连续观察骨骼肌、周围神经的电生理和组织病理变化。结果 :持续缺血 3小时后 ,再灌注损伤的病理变化在第 3天时最明显 ,预处理的保护作用此时最突出 ;而在电生理方面此时却表现为损伤后的逐渐恢复状态。结论 :止血带缺血预处理对骨骼肌和周围神经的缺血再灌注损伤有明显保护作用 ,电生理变化是监测肢体缺血再灌注损伤与恢复的敏感和确切指标。     

β-七叶皂甙钠对肢体缺血再灌注损伤的保护作用

目的 :观察 β -七叶皂甙钠对肢体缺血再灌注损伤的保护作用。 方法 :用兔造成肢体缺血再灌注损伤动物模型。实验分对照组、缺血再灌注组和β -七叶皂甙钠组。取血浆测定丙二醛、肌酸磷酸激酶、谷草转氨酶和乳酸脱氢酶含量。取骨骼肌标本测定丙二醛、髓过氧化酶活性、肌细胞线粒体钙含量和组织湿 /干重比值。结果 :缺血再灌注组与对照组比较 ,血浆和骨骼肌各项生化指标显著增高 (P <0 .0 1) ;使用 β -七叶皂甙钠后 ,血浆及骨骼肌各项测定指标较缺血再灌注组相比明显降低 (P<0 .0 5 ,P <0 .0 1)。结论 :β -七叶皂甙钠可减轻肢体缺血再灌注损伤 ,对骨骼肌有保护使用     

β—七叶皂甙钠对肢体缺血再灌注损伤的保护作用

目的 观察β－七叶皂甙钠对肢体缺血再灌注损伤的保护作用。方法 用兔造成肢体缺血再灌注损伤动物模型。实验分对照组、缺血再灌注组和β－七叶皂甙钠组。取血浆测定丙二醛、肌酸磷酸激酶、谷草转氨酶和乳酸脱氢酶含量。取骨骼肌标本测定丙二醛、髓过氧化酶活性、肌细胞线粒体钙含量和组织湿／干重比值。结果 缺血再灌注组与对照组比较，血 浆和骨骼肌各项生化指标显著增高（Ｐ〈０．０１）；使用β－七叶皂甙钠后，血浆及骨骼肌     

肢体缺血再灌注引起骨骼肌内皮素表达上调的实验研究

骨骼肌缺血后出现再灌注损伤[1 ] 。各种因素所致血管痉挛是引起再灌注损伤的因素[2 ] 。内皮素 (ＥＴ)是一种强烈的血管收缩肽[3 ] ,研究表明 ,它参与了心肌缺血再灌注损伤[4] 。对于内皮素与骨骼肌缺血再灌注损伤的关系少有报道[2 ,5 ] 。笔者应用放免及免疫组化技术 ,以明确大鼠肢体缺血再灌注后不同时相点ＥＴ- 1在肌肉及血浆中的变化规律 ,为研究ＥＴ与骨骼肌缺血再灌注损伤的关系提供依据。一、材料与方法1.动物模型 :ＳＤ大鼠 30只 ,体重30 0～ 40 0ｇ ,随机分为 5组 ,即假手术组、缺血组、再灌注 2 ,2 4,48ｈ组 ,每组 6只。水合氯醛…     

止血带缺血预处理对大鼠骨骼肌缺血再灌注损伤的保护作用--组织病理学研究

目的 :研究止血带缺血预处理对骨骼肌缺血再灌注损伤的保护作用和缺血时间梯度与再灌注时间梯度的关系。方法 :选择健康SD大鼠 12 0只 ,随机分成缺血预处理组 (实验组 )和非预处理组 (对照组 )。每组再分为缺血 2小时、3小时、4小时 3个小组 ,每小组 2 0只。用特制的气囊止血带制成大鼠后肢缺血再灌注损伤模型 ,通过连续切片观察预处理组与非预处理组大鼠胫前肌和股四头肌在不同缺血时间及不同再灌注时间发生的病理变化 ,评价止血带缺血预处理对大鼠骨骼肌缺血再灌注损伤的保护作用 ,探讨缺血时间梯度与再灌注时间梯度的关系。结果 :缺血 2小时 ,预处理组与非预处理组骨骼肌病理变化轻 ,保护作用不明显。缺血 3小时 ,两组均发生明显病理变化。无论在炎细胞浸润 ,还是肌细胞变性坏死 ,对照组均明显重于实验组 ,保护作用显著。缺血 4小时 ,两组病理损害十分严重 ,保护作用不如缺血 3小时明显。从再灌注第 1、3、7、14天的病理结果比较发现 ,再灌注第 3天时病理损伤最重 ,保护作用最明显。结论 :止血带缺血预处理对骨骼肌缺血再灌注损伤具有明显保护作用 ,尤其对缺血 3小时再灌注 3天时保护作用最显著 ,缺血超过一定时间则保护作用不明显     

马来酸桂哌齐特对骨胳肌缺血-再灌注损伤的保护作用与机制研究

目的探讨马来酸桂哌齐特对骨胳肌缺血再灌注损伤的保护作用及其机制。方法♂Wistar大鼠56只，随机分为假手术组（s组）、缺血再灌注组（I／R组）、马来酸桂哌齐特组（T组），检测骨骼肌腺苷含量和肿瘤坏死因子（TNF）-α基因转录水平，观察骨骼肌线粒体超微结构变化。结果I／R组缺血后20min骨骼肌腺苷含量显著升高，缺血2h和再灌注后1h明显回降，T组缺血后20min骨骼肌腺苷含量与I／R组无显著差异，但在缺血2h和再灌注后1h分别显著高于I／R组（P〈0．01）。I／R组再灌注1h骨骼肌TNF-α基因转录水平显著升高，T组显著低于I／R组（P〈0．01）。T组骨骼肌线粒体损伤明显轻于I／R组。结论马来酸桂哌齐特能够通过增加腺苷含量和抑制炎症反应，减轻骨骼肌缺血-再灌注损伤。     

补体在缺血再灌注损伤中的作用及机制

补体系统在缺血再灌注时通过多种途径被激活,形成大量的活化片段.这些片段在缺血再灌注损伤中发挥着重要作用,它们通过直接作用和对白细胞与内皮细胞的间接作用造成组织器官损伤.目前抗补体的药物虽较多,但真正用于临床的十分有限.笔者现就缺血再灌注时补体的激活途径,活化补体成分引起损伤的作用机制及防治研究进展综述如下.     

醛固酮在大鼠骨骼肌缺血再灌注所致心肌损伤中的变化

目的 观察醛固酮(ALD)在骨骼肌缺血再灌注所致心肌损伤中的动态变化.方法 雄性wistar大鼠62只,应用止血带结扎构建大鼠双下肢缺血再灌注模型,按照缺血及再灌注不同时间点随机分为以下9组:正常对照组(n=8),缺血2h组(n=4),缺血4h组(n=8),再灌注0.5h组(n=8),再灌注2h组(n=8),再灌注4h组(n=8),再灌注6h组(n=8),再灌注12h组(n=4),再灌注24h组(n=6),其中再灌注组缺血时间均为4h.观察各组大鼠血浆ALD、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肌钙蛋白-T(TNT)及心肌ALD水平的变化.结果 与正常对照组比较,缺血4h组血浆及心肌ALD水平开始上升(P<0.05),再灌注后二者继续上升.再灌注24h组血浆ALD达峰值,是正常对照组的6.2倍,且明显高于再灌注4h组(P<0.05),再灌注4～24h,心肌ALD持续稳定在较高水平;与缺血4h组比较,再灌注4、6、12、24h各组血浆及心肌ALD水平均明显升高(P<0.05).与正常对照组比较,缺血2h后血浆CK-MB即开始明显上升,缺血4h后血浆TNT、LDH开始升高(P0.05);再灌注后,上述心肌酶学指标继续上升,于再灌注4～6h达峰值,且明显高于缺血组(P<0.05).结论 骨骼肌缺血再灌注可导致全身及心肌局部醛固酮的持续激活,可能对骨骼肌缺血再灌注后远期心肌结构及功能损伤具有重要作用.     

体外循环法对犬骨骼肌缺血再灌注损伤的保护作用

 目的 探讨体外循环法(extracorporeal circulation, ECC)对犬骨骼肌缺血再灌注损伤的保护作用。方法 首先建立犬骨骼肌缺血再灌注损伤模型,通过HE染色法观察组织炎性细胞浸润,利用TUNEL法观察组织凋亡的变化,特异性试剂盒检测LD、SOD等酶的变化,ELISA法检测IL-10和TNF-α等细胞因子的变化,评价ECC法再灌注模式对犬骨骼肌缺血再灌注损伤的保护作用。结果 模型组动物的组织炎性细胞浸润明显,诱导细胞凋亡发生,血清中LD[(2.6±0.3)mmol/ml vs.(5.2±0.1)mmol/ml ]、SOD[(15.2±1.2)U/ml vs.(31.1±2.1)U/ml]等酶的水平显著增加,同时血清中IL-10[(60.4±2.3)pg/ml vs.(89.2±1.5)pg/ml ]和TNF-α[(172.3±8.7)ng/l vs. (273.4±12.5 )ng/l]等细胞因子的含量显著增加 (P<0.01)。ECC法再灌注处理的动物,其组织炎性反应和细胞凋亡程度显著低于模型组动物,血清中上述酶和细胞因子的水平也显著降低,分别为:LD[(3.5±0.1)mmol/ml vs. (5.2±0.1) mmol/ml],SOD[(21.3±1.3)U/ml vs. (31.1±2.1) U/ml], IL-10[(69.4±2.6) pg/ml vs. (89.2±1.5)pg/ml]和TNF-α[(190.8±12.1)ng/l vs.(273.4±12.5)ng/l ](P<0.05)。结论 ECC法再灌注模式,对犬骨骼肌缺血再灌注损伤具有一定的保护作用。     

犬肺栓塞缺血-再灌注损伤模型的实验研究

目的 建立一种良好的适合进行影像学实验研究的肺栓塞缺血-再灌注损伤动物模型.方法 健康杂种犬20只.采用Seldinger技术穿刺右颈内静脉,置鞘,经鞘置入Swan-Ganz导管,用其球囊栓塞犬的右肺下叶动脉4 h,然后再撤除球囊,使血流再灌注4 h,制成肺栓塞缺血-再灌注损伤模型.在缺血前、缺血4 h和再灌注4 h 3个时间点进行肺部CT扫描.最后处死犬,把双下叶肺组织送检病理和电镜检查.结果 成功制作20只犬的闭胸式活体肺栓塞缺血-再灌注损伤模型,CT、病理和电镜扫描显示均符合肺栓塞缺血-再灌注损伤的变化,即渗透性肺水肿.结论 犬的闭胸式活体肺栓塞缺血-再灌注损伤模型可真实模拟肺栓塞缺血-再灌注损伤的病理生理过程,是一种良好的适合进行影像学实验研究的动物模型.     

Engineered muscle: a tool for studying muscle physiology and function

Recent advances in skeletal muscle tissue engineering have resulted in an in vitro tissue model that can be used for studying the effects of genetic alterations, pharmacological interventions, and exercise on muscle physiology and function. Here, we present applications for this technology to further our understanding of the molecular mechanisms underlying skeletal muscle adaptation in response to exercise.     

The role of apoptosis in age-related skeletal muscle atrophy

Skeletal myocyte atrophy and death contribute to sarcopenia, a condition associated with normal aging. By 80 years of age, it is estimated that humans generally lose 30-40% of skeletal muscle fibres. The mechanism for this loss is unknown; however, it may involve apoptosis. Mitochondrial dysfunction and sarcoplasmic reticulum (SR) stress that occurs with age may be possible stimuli inducing apoptosis. Hence, mitochondria and SR may be important organelles within skeletal myocytes responsible for apoptosis signalling. The activation of apoptosis may be partly responsible for the initiation of muscle protein degradation, loss of muscle nuclei associated with local atrophy, and cell death of the myocyte. Exercise training and caloric restriction are two interventions known to enhance skeletal muscle function. The effects of these interventions on apoptosis are discussed.     

Adaptations to training in endurance cyclists: implications for performance.

Our present scientific knowledge of the effects of specific training interventions undertaken by professional cyclists on selected adaptive responses in skeletal muscle and their consequences for improving endurance performance is limited: sport scientists have found it difficult to persuade elite cyclists to experiment with their training regimens and access to muscle and blood samples from these athletes is sparse. Owing to the lack of scientific study we present a theoretical model of some of the major training-induced adaptations in skeletal muscle that are likely to determine performance capacity in elite cyclists. The model includes, but is not limited to, skeletal muscle morphology, acid-base status and fuel supply. A working premise is that the training-induced changes in skeletal muscle resulting from the high-volume, high-intensity training undertaken by elite cyclists is at least partially responsible for the observed improvements in performance. Using experimental data we provide evidence to support the model.     

Nutritional interventions to promote post-exercise muscle protein synthesis

Resistance exercise is a powerful stimulus to augment muscle protein anabolism, as it can improve the balance between muscle protein synthesis and breakdown. However, the intake of food during post-exercise recovery is necessary for hypertrophy to occur. Therefore, athletes need to ingest protein following exercise to attain a positive protein balance and maximise their skeletal muscle adaptive response. The interaction between exercise and nutrition is not only important for athletes, but is also of important clinical relevance in the elderly. Exercise interventions combined with specific nutritional modulation provide an effective strategy to counteract or reduce the loss of skeletal muscle mass with aging.     

6周负重跑训练和补充大豆多肽对D-半乳糖衰老大鼠骨骼肌IGF-I mRNA和GDF-8 mRNA表达的影响

目的:探讨6周负重跑训练和补充大豆多肽对衰老大鼠骨骼肌IGF-I mRNA和GDF-8 mRNA表达的影响。方法:56只雄性SD大鼠随机分为7组:成年组,模型组,大负重组,小负重组,补肽组,补肽+大负重组和补肽+小负重组。除成年组外,其余各组大鼠采用6周D-半乳糖皮下注射复制亚急性骨骼肌衰老模型,同时按分组分别施加大(70%最大负重)、小(30%最大负重)两种负重方式的跑台训练或/和补充15%大豆多肽的干预。6周实验结束后禁食12小时,处死所有大鼠,无菌取材,测试骨骼肌IGF-I mRNA和GDF-8mRNA表达量。结果:与成年组相比,模型组骨骼肌IGF-I mRNA表达显著下降(P<0.01),GDF-8 mRNA表达显著升高(P<0.01),负重或补肽单独干预及其联合干预均可有效逆转以上趋势(P<0.01),并且负重和补肽两者具有显著交互作用。结论:负重跑训练或补充大豆多肽干预,可有效改善衰老大鼠骨骼肌IGF-I mRNA低表达和GDF-8 mRNA高表达,并且两种手段联合运用也可达到相同效果。     

Weight loss and exercise: implications for muscle lipid metabolism and insulin action

Implications for Muscle Lipid Metabolism and An accumulation of intramuscular lipid has been reported with obesity and linked with insulin resistance. The purpose of this paper is to discuss: 1) mechanisms that may be responsible for intramuscular lipid accumulation with obesity, and 2) the effects of common interventions (weight loss or exercise) for obesity on skeletal muscle lipid metabolism and intramuscular lipid content. Data suggest that the skeletal muscle of morbidly obese humans is characterized by the preferential partitioning of lipid toward storage rather than oxidation. This phenotype may, in part, contribute to increased lipid deposition in both muscle and adipose tissue, and promote the development of morbid obesity and insulin resistance. Weight loss intervention decreases intramuscular lipid content, which may contribute to improved insulin action. On the other hand, exercise training improves insulin action and increases fatty acid oxidation in the skeletal muscle of obese/morbidly obese individuals. In summary, the accumulation of intramuscular lipid appears to be detrimental in terms of inducing insulin resistance; however, the accumulation of lipid can be reversed with weight loss. The mechanism(s) by which exercise enhances insulin action remains to be determined.     

The molecular bases of training adaptation

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.     

Skeletal muscle: microcirculatory adaptation to metabolic demand

The issue of whether skeletal muscle is master or slave of the cardiovascular system depends on frame of reference. Acute manipulations of convective O2 delivery clearly show that O2 supply sets the upper limit of muscle VO2max. However, studies of adaptation to chronic conditions such as training and hypoxia show that skeletal muscle has a remarkable capacity to meet changes in metabolic demand. Moreover, there are several lines of evidence that these adaptations are essential to changes in VO2max. Studies show that with training, electrical stimulation, and chronic hypoxia, the ratio of capillary surface per fiber surface and fiber mitochondrial volume/fiber length is preserved, suggesting a primary regulated feature in skeletal muscle is matching the structural capacity for O2 flux to mitochondrial metabolic demand. Adaptations in both capillarity and mitochondrial respiratory capacity have also been shown to be important components in the adaptive increase in VO2max with training. Collectively, this evidence argues against skeletal muscle being simply a slave to the cardiovascular system.     

Effect of muscular activity on the turnover rate of actin and myosin heavy and light chains in different types of skeletal muscle.

In endurance-trained rats the myosin HC have a more rapid turnover rate than in control animals in all three types of skeletal muscle fibres, but in sprint-trained rats only in fast-glycolytic and fast-oxidative-glycolytic fibres. A comparison of the actin turnover rate in sprint- and endurance-trained animals shows that in both groups there are more rapid turnover rates in all types of muscle fibres in comparison with control rats. During long-lasting exhaustive exercise the turnover rate of myosin HC decreases. Twelve hours after exercise, myosin LC 2 and 3, and actin have a more rapid turnover than in control rats. Changes in the turnover rate of muscle contractile proteins during exercise and the recovery period after exercise reflect the functional conditions of the contractile apparatus in different types of skeletal muscle fibres and have a physiological significance.