有氧运动对高糖高脂膳食大鼠腓肠肌Nrf2-SOD的影响*

目的: 探讨有氧运动预防大鼠胰岛素抵抗中Nrf2及SOD的变化。方法: 24只12月龄SD大鼠随机分为对照组(C)、高糖高脂IR组(IR)和高糖高脂IR并运动组(IRE)。IRE进行递增负荷跑台运动,运动6周。检测腓肠肌T-SOD、CAT、MDA、GSH/GSSG,ELISA法检测腓肠肌8-OHdG含量,Western blot检测腓肠肌Nrf2和GLUT4表达。结果: ①IRE组HOMA-IR明显低于IR组(P＜0.05);IRE组肌糖原明显高于IR组(P＜0.01);②IRE组T-SOD和CAT、GSH/GSSG明显高于IR组(P＜0.01);IRE组8-OHdG和MDA明显低于IR组(P＜0.01);③IRE组腓肠肌Nrf2和GLUT4明显高于IR组 (P＜0.01) 。结论: 有氧运动可激活大鼠腓肠肌Nrf2-SOD通路,提高抗氧化酶活性和糖摄取能力,预防IR发生。     

Relationship between resting medial gastrocnemius stiffness and drop jump performance

Although the influence of the series elastic element of the muscle–tendon unit on jump performance has been investigated, the corresponding effect of the parallel elastic element remains unclear. This study examined the relationship between the resting calf muscle stiffness and drop jump performance. Twenty-four healthy men participated in this study. The shear moduli of the medial gastrocnemius and the soleus were measured at rest as an index of muscle stiffness using ultrasound shear wave elastography. The participants performed drop jumps from a 15 cm high box. The Spearman rank correlation coefficient was used to examine the relationships between shear moduli of the muscles and drop jump performance. The medial gastrocnemius shear modulus showed a significant correlation with the drop jump index (jump height/contact time) (r = 0.414, P = 0.044) and jump height (r = 0.411, P = 0.046), but not with contact time (P > 0.05). The soleus shear modulus did not correlate with these jump parameters (P > 0.05). These results suggest that the resting medial gastrocnemius stiffness can be considered as one of the factors that influence drop jump performance. Therefore, increase in resting muscle stiffness should enhance explosive athletic performance in training regimens.     

Role of gastrocnemius activation in knee joint biomechanics: gastrocnemius acts as an ACL antagonist

Gastrocnemius is a premier muscle crossing the knee, but its role in knee biomechanics and on the anterior cruciate ligament (ACL) remains less clear when compared to hamstrings and quadriceps. The effect of changes in gastrocnemius force at late stance when it peaks on the knee joint response and ACL force was initially investigated using a lower extremity musculoskeletal model driven by gait kinematics—kinetics. The tibiofemoral joint under isolated isometric contraction of gastrocnemius was subsequently analyzed at different force levels and flexion angles (0°–90°). Changes in gastrocnemius force at late stance markedly influenced hamstrings forces. Gastrocnemius acted as ACL antagonist by substantially increasing its force. Simulations under isolated contraction of gastrocnemius confirmed this role at all flexion angles, in particular, at extreme knee flexion angles (0° and 90°). Constraint on varus/valgus rotations substantially decreased this effect. Although hamstrings and gastrocnemius are both knee joint flexors, they play opposite roles in respectively protecting or loading ACL. Although the quadriceps is also recognized as antagonist of ACL, at larger joint flexion and in contrast to quadriceps, activity in gastrocnemius substantially increased ACL forces (anteromedial bundle). The fact that gastrocnemius is an antagonist of ACL should help in effective prevention and management of ACL injuries.     

Free radical generation by skeletal muscle of adult and old mice: effect of contractile activity

Oxidative modification of cellular components may contribute to tissue dysfunction during aging. In skeletal muscle, contractile activity increases the generation of reactive oxygen and nitrogen species (ROS). The question of whether contraction-induced ROS generation is further increased in skeletal muscle of the elderly is important since this influences recommendations on their exercise participation. Three different approaches were used to examine whether aging influences contraction-induced ROS generation. Hind limb muscles of adult and old mice underwent a 15-min period of isometric contractions and we examined ROS generation by isolated skeletal muscle mitochondria, ROS release into the muscle extracellular fluid using microdialysis techniques, and the muscle glutathione and protein thiol contents. Resting skeletal muscle of old mice compared with adult mice showed increased ROS release from isolated mitochondria, but no changes in the extracellular levels of superoxide, nitric oxide, hydrogen peroxide, hydroxyl radical activity or muscle glutathione and protein thiol contents. Skeletal muscle mitochondria isolated from both adult and old mice after contractile activity showed significant increases in hydrogen peroxide release compared with pre-contraction values. Contractions increased extracellular hydroxyl radical activity in adult and old mice, but had no significant effect on extracellular hydrogen peroxide or nitric oxide in either group. In adult mice only, contractile activity increased the skeletal muscle release of superoxide. A similar decrease in muscle glutathione and protein thiol contents was seen in adult and old mice following contractions. Thus, contractile activity increased skeletal muscle ROS generation in both adult and old mice with no evidence for an age-related exacerbation of ROS generation.     

An innovative solution to reduce muscle deformation during ultrasonography data collection

Background3D freehand ultrasound enables the creation of volumetric data. The acquisition of morphological features, such as muscle volume, is influenced by the variations in force applied to the skin with the ultrasound probe. To minimise the deformations, a concave-shaped plastic mount combined with a custom-shaped gel pad was developed for the ultrasound head, named Portico. This study analyses to what extent the Portico reduces muscle deformation and corresponding errors in estimating muscle volume.MethodTwenty medial gastrocnemius (MG) muscles were assessed (10 from typically developing children; 10 from children with spastic cerebral palsy). Two repetitions were acquired in each of the following approaches: (1) with the lower leg submerged in a water tank as a non-deformed reference; (2) probe-on-skin (PoS) as the conventional approach and (3) the newly introduced Portico. PoS and Portico data were registered with respect to the ones corresponding in a water tank. An in-house software package (Py3DFreeHandUS) was used to process the data and MG volume was estimated using MeVisLab. The minimal detectable change (MDC) was calculated.ResultsWith respect to the PoS approach, the Portico reduced muscle deformation by 46%. For both the typically developing and spastic cerebral palsy cohorts, lower MDCs were found when using the Portico.DiscussionDespite the improvements, the Portico did not yield statistically more reliable MG volume estimations than the traditional PoS approach. Further improvement can be attained by optimising the fit between the gel pad and the curvature of the limb, using a larger choice of Portico geometries.     

Sensory pathways and their modulation in the control of locomotion

Recent experiments have extended our understanding of how sensory information in premotor networks controlling motor output is processed during locomotion, and at what level the efficacy of specific sensory—motor pathways is determined. Phasic presynaptic inhibition of sensory transmission combined with postsynaptic alterations of excitatory and inhibitory synaptic transmission from interneurons of the premotor networks contribute to the modulation of reflex pathways and to the generation of reflex reversal. These mechanisms play an important role in adapting the operation of central networks to external demands and thus help optimize sensory—motor integration.     

Neuronal growth regulator 1 promotes adipocyte lipid trafficking via interaction with CD36

Neuronal growth regulator 1 (NEGR1) is a glycosylphosphatidylinositol-anchored membrane protein associated with several human pathologies, including obesity, depression, and autism. Recently, significantly enlarged white adipose tissue, hepatic lipid accumulation, and decreased muscle capacity were reported in Negr1-deficient mice. However, the mechanism behind these phenotypes was not clear. In the present study, we found NEGR1 to interact with cluster of differentiation 36 (CD36), the major fatty acid translocase in the plasma membrane. Binding assays with a soluble form of NEGR1 and in situ proximal ligation assays indicated that NEGR1-CD36 interaction occurs at the outer leaflet of the cell membrane. Furthermore, we show that NEGR1 overexpression induced CD36 protein destabilization in vitro. Both mRNA and protein levels of CD36 were significantly elevated in the white adipose tissue and liver tissues of Negr1^?/? mice. Accordingly, fatty acid uptake rate increased in NEGR1-deficient primary adipocytes. Finally, we demonstrated that Negr1^?/? mouse embryonic fibroblasts showed elevated reactive oxygen species levels and decreased adenosine monophosphate-activated protein kinase activation compared with control mouse embryonic fibroblasts. Based on these results, we propose that NEGR1 regulates cellular fat content by controlling the expression of CD36.     

Comparative proteomic profiling reveals a role for Cisd2 in skeletal muscle aging

Skeletal muscle has emerged as one of the most important tissues involved in regulating systemic metabolism. The gastrocnemius is a powerful skeletal muscle composed of predominantly glycolytic fast‐twitch fibers that are preferentially lost among old age. This decrease in gastrocnemius muscle mass is remarkable during aging; however, the underlying molecular mechanism is not fully understood. Strikingly, there is a ~70% decrease in Cisd2 protein, a key regulator of lifespan in mice and the disease gene for Wolfram syndrome 2 in humans, within the gastrocnemius after middle age among mice. A proteomics approach was used to investigate the gastrocnemius of naturally aged mice, and this was compared to the autonomous effect of Cisd2 on gastrocnemius aging using muscle‐specific Cisd2 knockout (mKO) mice as a premature aging model. Intriguingly, dysregulation of calcium signaling and activation of UPR/ER stress stand out as the top two pathways. Additionally, the activity of Serca1 was significantly impaired and this impairment is mainly attributable to irreversibly oxidative modifications of Serca. Our results reveal that the overall characteristics of the gastrocnemius are very similar when naturally aged mice and the Cisd2 mKO mice are compared in terms of pathological alterations, ultrastructural abnormalities, and proteomics profiling. This suggests that Cisd2 mKO mouse is a unique model for understanding the aging mechanism of skeletal muscle. Furthermore, this work substantiates the hypothesis that Cisd2 is crucial to the gastrocnemius muscle and suggests that Cisd2 is a potential therapeutic target for muscle aging.     

缺氧习服对冻伤大鼠骨骼肌耗氧量的影响

目的与方法使用生物组织氧耗测量系统测定了常氧冻伤(FN)、急性缺氧冻伤(FAH)和缺氧习服缺氧冻伤(FHAC)大鼠后肢重度冻伤前后腓肠肌耗氧量的变化,以探讨缺氧习服加重冻伤组织损伤的机理.结果冻前,FHAC组腓肠肌耗氧量降低26.2%.冻后1d,FN、FAH和FHAC组腓肠肌耗氧量为5.93±0.66,4.74±1.87和0.76±0.39[kPa/(g*min)],分别较各自冻前水平降低76.3%,77.9%和95.9%,FHAC组明显低于其余两组;冻后5d三组的耗氧量分别恢复至各自冻前水平的62.8%、44.9%和28.8%,FHAC组仍明显低于其余两组,提示缺氧习服冻伤后骨骼肌代谢率降低更明显,恢复更缓慢.结论缺氧习服和冻伤均使腓肠肌耗氧量明显减少,二者的叠加使缺氧习服大鼠冻后腓肠肌耗氧量进一步降低,表明组织代谢的变化是影响冻伤组织损伤及修复的主要因素之一.     

A Framework for Structured Modeling of Skeletal Muscle

The aim of this study is to present a detailed continuum mechanics formulation, and the corresponding algorithms, to predict the deformation of skeletal muscle at different structural levels, starting from the muscle fiber level. The model is used to investigate force production and structural changes during isometric and dynamic contractions of the cat medial gastrocnemius. From a comparison with experimental data obtained in our own laboratories, we conclude that the model faithfully predicts all of the observations pertaining to force production, fascicle length and angle of pennation under various test conditions.