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比较褪黑素和催产素在预防实验性脓毒症大鼠危重病性多发性神经病中的作用。

Comparison of melatonin and oxytocin in the prevention of critical illness polyneuropathy in rats with experimentally induced sepsis.

机构信息

Department of Physiology, Ege University School of Medicine, Izmir, Turkey.

出版信息

J Surg Res. 2013 Jul;183(1):313-20. doi: 10.1016/j.jss.2012.11.043. Epub 2012 Dec 8.

DOI:10.1016/j.jss.2012.11.043
PMID:23312812
Abstract

BACKGROUND

Critical illness polyneuropathy is an acute neuromuscular disorder of critically ill patients and is characterized by limb and respiratory muscle weakness. The purpose of the study was to evaluate the neuroprotective effects of melatonin (MEL) and oxytocin (OT) on the early stage of sepsis by recording compound muscle action potentials and measuring plasma tumor necrosis factor (TNF)-α levels, lipid peroxidation (malondialdehyde; MDA), and total antioxidant capacity.

MATERIALS AND METHODS

One hundred adult male Sprague-Dawley rats were included in the study. The cecal ligation and puncture (CLP) procedure was performed to induce the sepsis model. MEL (10, 20, and 40 mg/kg), OT (0.4, 0.8, and 1.6 mg/kg), and a combination of MEL (20 mg/kg) and OT (0.8 mg/kg) were administered intraperitoneally in the first hour of surgery. Electromyography (EMG) studies were achieved 24 h after CLP surgery and then blood samples were collected for biochemical measurements.

RESULTS

EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the CLP group compared with the sham group (P < 0.05 and P < 0.0005). Moreover, the animals that received CLP surgery showed significantly higher TNF-α and MDA levels and lower total antioxidant capacity values than the sham group. The administration of MEL and OT to rats significantly abolished the EMG alterations and suppressed oxidative stress and TNF-α release in CLP-induced rats.

CONCLUSIONS

The inflammatory processes and imbalance in oxidative/antioxidative status play important roles in the pathogenesis of critical illness polyneuropathy. We suggest that both oxytocin and melatonin may have beneficial effects against sepsis-induced polyneuropathy in critical illness.

摘要

背景

危重病性多发性神经病是危重病患者的一种急性神经肌肉疾病,其特征为四肢和呼吸肌无力。本研究的目的是通过记录复合肌肉动作电位并测量血浆肿瘤坏死因子(TNF)-α 水平、脂质过氧化(丙二醛;MDA)和总抗氧化能力来评估褪黑素(MEL)和催产素(OT)对脓毒症早期的神经保护作用。

材料和方法

本研究纳入了 100 只成年雄性 Sprague-Dawley 大鼠。采用盲肠结扎穿孔(CLP)程序建立脓毒症模型。MEL(10、20 和 40mg/kg)、OT(0.4、0.8 和 1.6mg/kg)以及 MEL(20mg/kg)和 OT(0.8mg/kg)联合用药于手术后 1 小时内腹腔内给药。CLP 手术后 24 小时进行肌电图(EMG)研究,然后采集血液样本进行生化测量。

结果

EMG 结果显示,与假手术组相比,CLP 组复合肌肉动作电位幅度显著降低,远端潜伏期延长(P<0.05 和 P<0.0005)。此外,接受 CLP 手术的动物 TNF-α 和 MDA 水平显著升高,总抗氧化能力值显著降低,与假手术组相比(P<0.05 和 P<0.0005)。褪黑素和催产素的给药可显著消除 EMG 改变,并抑制 CLP 诱导的大鼠氧化应激和 TNF-α 释放。

结论

炎症过程和氧化/抗氧化状态失衡在危重病性多发性神经病的发病机制中发挥重要作用。我们认为,催产素和褪黑素都可能对脓毒症引起的危重病性多发性神经病具有有益作用。

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