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缺乏半胱天冬酶-3 可减轻固定引起的肌肉萎缩和张力丧失,同时减轻细胞凋亡和炎症。

Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation.

机构信息

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Room 206, 5l Blossom Street, Boston, Massachusetts 02114, USA.

出版信息

Muscle Nerve. 2013 May;47(5):711-21. doi: 10.1002/mus.23642. Epub 2013 Feb 9.

Abstract

INTRODUCTION

Immobilization by casting induces disuse muscle atrophy (DMA).

METHODS

Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis, and inflammation during DMA.

RESULTS

Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius.

CONCLUSIONS

Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways.

摘要

简介

石膏固定会导致废用性肌肉萎缩(DMA)。

方法

使用野生型(WT)和半胱天冬酶-3 敲除(KO)小鼠,我们评估了半胱天冬酶-3 在 DMA 期间对肌肉质量、细胞凋亡和炎症的影响。

结果

半胱天冬酶-3 缺乏显著减轻了肌肉质量的减少[比目鱼肌:KO 组为 28±1%,WT 组为 41±3%;比目鱼肌:KO 组为 47±2%,WT 组为 56±2%(P<0.05)]和腓肠肌抽搐张力的减少(KO 组为 23±4%,WT 组为 36±3%,P<0.05)在固定侧与对侧后肢的第 14 天。缺乏半胱天冬酶-3 降低了固定诱导的比目鱼肌中凋亡肌核的增加(增加 3.2 倍)和巨噬细胞浸润(增加 2.2 倍),并减弱了腓肠肌中单核细胞趋化蛋白-1mRNA 表达的增加(KO 组为 2 倍,WT 组为 18 倍)。

结论

半胱天冬酶-3 在 DMA 及其相关张力下降中起关键作用,可能通过作用于细胞凋亡和炎症途径。

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