Neuromuscular Electrical Stimulation Improves Energy Substrate Metabolism and Survival in Mice With Acute Endotoxic Shock

Neuromuscular Electrical Stimulation Improves Energy Substrate Metabolism and Survival in Mice With Acute Endotoxic Shock
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神经肌肉电刺激改善急性内毒素休克小鼠的能量底物代谢和生存

DOI:
10.1097/shk.0000000000001354
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发表时间:
2020
期刊:
Shock (Augusta, Ga.)
影响因子:
--
通讯作者:
H. Yokota
H. Yokota
中科院分区:
--
文献类型:
--
作者:
T. Irahara;N. Sato;K. Otake;S. Murata;Kazuo Inoue;K. Koike;H. Yokota

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摘要本研究调查了神经肌肉电刺激(NMES)的治疗益处。通过腹膜内注射向C57 BL/6小鼠施用脂多糖(LPS; 20 mg/kg体重),并将其分为对照组(C)和NMES组(每组n=10-12)。  后者在低频或高频(LF = 2 Hz和HF = 50 Hz)和低压或高压(LV = 10 V和HV = 50 V)下接受双侧腓肠肌NMES 1 h。             在LF-LV和LF-HV组中,进行两次NMES,并将结果与接受一轮NMES的小鼠的结果进行比较。通过间接量热法测量24小时内能量代谢的变化 ,评价 LPS给药后72小时内的存活率;采用定量PCR检测肝脏和腓肠肌过氧化物酶体增殖物激活受体γ辅激活因子(PGC)-1α的表达,酶联免疫吸附试验检测血浆白细胞介素(IL)-6的浓度。仅LF-LV组和LF-HV组的生存率在1轮NMES(P < 0.01)和2轮NMES(P < 0.05)中有所改善。这两组的脂肪酸氧化(FAO)略有增加,而碳水化合物氧化(CHO)减少或没有变化。两组大鼠肌肉组织中PGC-1α表达显著上调,血浆IL-6水平显著降低(P < 0.05)。因此,NMES在通过PGC-1α上调和抑制炎症诱导能量代谢从葡萄糖为主代谢轻度转换为脂质为主代谢的条件下发挥治疗作用,并且即使在血流动力学不稳定的患者中也可能是有效的早期干预。
ABSTRACT This study investigated the therapeutic benefits of neuromuscular electrical stimulation (NMES). C57BL/6 mice were administered lipopolysaccharide (LPS; 20 mg/kg body weight) by intraperitoneal injection and divided into control (C) and NMES groups (n = 10–12 each). The latter received NMES to the bilateral gastrocnemius muscle for 1 h at low or high frequency (LF = 2 Hz and HF = 50 Hz, respectively) and low or high voltage (LV = 10 V and HV = 50 V, respectively). In LF–LV and LF–HV groups, NMES was performed twice and the results were compared with those for mice that received one round of NMES. Changes in energy metabolism were measured by indirect calorimetry up to 24 h; survival was evaluated up to 72 h after LPS administration; peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α expression in the liver and gastrocnemius muscle was evaluated by quantitative PCR; and plasma concentration of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay. Survival was improved only in the LF–LV group with one round of NMES (P < 0.01) and the LF–HV group with two rounds of NMES (P < 0.05). Fatty acid oxidation (FAO) was slightly increased in these two groups, whereas carbohydrate oxidation (CHO) was decreased or not changed. Significant upregulation of PGC-1α in muscle as well as a decrease in plasma IL-6 level were also observed in these two groups (P < 0.05). Thus, NMES exerts therapeutic effects under conditions that induce a mild switch in energy metabolism from glucose to lipid predominant metabolism through PGC-1α upregulation and suppression of inflammation, and may be an effective early intervention even in hemodynamically unstable patients.