衰竭性运动后的最大通气量

在剧烈运动中,通气肌是否出现疲劳和机能能力下降,这是有争论的。Fregosi 等报道过在衰竭性赛跑运动中,鼠的膈肌中乳酸急剧增加。Bye 等也指出在进行高强度短时间的运动之后,膈肌的最大跨壁压力降低。是这些变化还是其它的变化致使剧烈运动中和运动后最大通气能力减弱,目前尚未清楚。在本研究中,我们企图通过测定在跑台上进行持续时间为3—10分钟或60分钟的衰竭性运动的最后几分钟和运动后的60秒随意最大通气量,来探查这     

Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency

Collagen VI is an extracellular matrix protein that forms a microfilamentous network in skeletal muscles and other organs. Inherited mutations in genes encoding collagen VI in humans cause two muscle diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy. We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy. The pathophysiological defects and mechanisms leading to the myopathic disorder were not known. Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis. We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis. These defects were reversible, as they could be normalized by plating Col6a1-/- myofibers on collagen VI or by addition of cyclosporin A (CsA), the inhibitor of mitochondrial permeability transition pore (PTP). Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo. These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention.