Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb.
Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb.
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DOI：
10.3389/fphys.2018.00244
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发表时间：
2018
影响因子：
4
通讯作者：
Li YL
中科院分区：
文献类型：
--
作者：
Corrick RM;Tu H;Zhang D;Barksdale AN;Muelleman RL;Wadman MC;Li YL
肢体损伤并出血一直是平民医疗和战场上死亡的一个重要原因。止血带作为治疗肢体损伤的介入手段是必要的；然而，止血带和随后的松开会导致骨骼肌和神经肌肉接头(NMJ)严重的急性缺血-再灌注(IR)损伤。大量证据表明，炎症是导致急性IR损伤的重要因素。为寻找止血带所致急性IR损伤的有效治疗措施，本研究观察了抗炎药地塞米松对止血带所致小鼠后肢急性IR损伤的影响。在C57/BL6小鼠的髋关节一侧后肢(左后肢)上放置止血带3h，然后松开24h以诱导IR。止血带3h、松开24h(24 H IR)可引起腓肠肌损伤，包括肌膜破裂和坏死(42.8±2.3%)。在NMJ，24小时IR小鼠运动神经末梢消失，终板电位检测不到。24小时IR组小鼠腓肠肌无收缩现象。免疫印迹结果显示，缺血再灌流24 h后，腓肠肌组织中炎性细胞因子(肿瘤坏死因子α和白介素1β)表达增加。再灌流开始时给予地塞米松(1 mg/kg，ip)。显著抑制肿瘤坏死因子α和IL-1β的表达，减少肌膜破裂和心肌梗死面积(2 4.8±2.0%)，改善直接肌肉刺激诱导的腓肠肌收缩。然而，这种抗炎药物并没有改善24小时IR小鼠的NMJ的形态和功能，也没有改善坐骨神经刺激的骨骼肌收缩。这些数据表明，在再灌流开始时一次性使用地塞米松仅减少了骨骼肌的结构和功能损伤，而不是通过抑制炎性细胞因子来减少NMJ的损伤。
Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR) injury in the skeletal muscle and neuromuscular junction (NMJ). Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb) at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR) caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle). In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1β) were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p.) significantly inhibited expression of TNFα and IL-1β, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%), and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the NMJ through inhibiting inflammatory cytokines.
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DOI：
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发表时间：
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影响因子：
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作者：
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发表时间：
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影响因子：
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