Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation-induced atrophy
Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation-induced atrophy
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DOI：
10.1164/rccm.200601-142oc
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发表时间：
2007-01-15
影响因子：
24.7
通讯作者：
Powers, Scott K.
中科院分区：
文献类型：
--
作者：
McClung, Joseph M.;Kavazis, Andreas N.;Powers, Scott K.
原理：通过机械通气（MV）卸载膈肌会导致快速的膈肌纤维萎缩。目前尚不清楚Mycobacteria域是否目的：我们通过半胱天冬酶-3介导的类凋亡机制检测了MV诱导的肌萎缩与肌核丢失相关的假设，该机制导致恒定的肌萎缩结构域。方法：为了验证这一假设，将Sprague-Dawley大鼠随机分配到对照组或暴露于6或12小时MV的实验组，其中施用或不施用半胱天冬酶。测量和主要结果：MV 12小时后，I型和IIa型膈肌肌纤维面积分别减少17%和23%，caspase-3抑制减弱了这种减少。横膈膜肌纤维含量下降后，12小时的MV，并导致在维护一个恒定的肌纤维结构域中的所有纤维类型。MV的6和12小时均导致膈肌中凋亡标志物的半胱天冬酶-3依赖性增加（例如，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞核和DNA片段化的数量）。6小时后发生的MV，肌纤维atrophic.Conclusions：总的来说，这些数据支持这一假设，即膈肌肌纤维的myocardial域维持在长期MV和caspase-3介导的myocardial细胞凋亡有助于这一过程。
Rationale: Unloading the diaphragm via mechanical ventilation (MV) results in rapid diaphragmatic fiber atrophy. It is unknown whether the myonuclear domain (cytoplasmic myofiber volume/ myonucleus) of diaphragm myofibers is altered during MV.Objective: We tested the hypothesis that MV-induced diaphragmatic atrophy is associated with a loss of myonuclei via a caspase-3-mediated, apoptotic-like mechanism resulting in a constant myonuclear domain.Methods:To test this postulate, Sprague-Dawley rats were randomly assigned to a control group or to experimental groups exposed to 6 or 12 h of MV with or without administration of a caspase-3 inhibitor.Measurements and Main Results: After 12 h of MV, type I and type Ila diaphragm myofiber areas were decreased by 17 and 23%, respectively, and caspase-3 inhibition attenuated this decrease. Diaphragmatic myonuclear content decreased after 12 h of MV and resulted in the maintenance of a constant myonuclear domain in all fiber types. Both 6 and 12 h of MV resulted in caspase-3-dependent increases in apoptotic markers in the diaphragm (e.g., number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive nuclei and DNA fragmentation). Caspase-3-dependent increases in apoptotic markers occurred after 6 h of MV, before the onset of myofiber atrophy.Conclusions: Collectively, these data support the hypothesis that the myonuclear domain of diaphragm myofibers is maintained during prolonged MV and that caspase-3-mediated myonuclear apoptosis contributes to this process.