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拉科酰胺改善作用的证明:在脓毒症诱导的危重病性多发性神经病大鼠模型中

Demonstration of ameliorative effect of lacosamide: in a rat model of sepsis-induced critical illness polyneuropathy.

作者信息

Solmaz Volkan, Aksoy Dürdane, Yılmaz Mustafa, Eser Enes, Erbas Oytun

出版信息

Neurol Res. 2015 Sep;37(9):797-802. doi: 10.1179/1743132815Y.0000000040. Epub 2015 Apr 28.

Abstract

OBJECTIVES

Critical illness neuropathy (CIN) is a condition that may occur in diseases with severe systemic response, particularly in sepsis. The aim of this study is to investigate the potential anti-inflammatory and lipid-peroxidation inhibiting activities of lacosamide by measuring tumour necrotizing factor-alpha (TNF-alpha), C-reactive protein (CRP), malondialdehyde (MDA) and white blood cells (WBC) using electroneuromyography (ENMG) in rats with sepsis-induced critical illness neuropathy (SICIN).

METHODS

Cecal ligation and puncture (CLP) procedure was performed on 39 rats to induce a sepsis model. The study groups were designed as follows: Group 1: normal (nonoperative); Group 2: (sham-operated); Group 3: CLP (untreated group); Group 4: CLP and lacosamide 20 mg/kg; Group 5: CLP and lacosamide 40 mg/kg. TNF-alpha, C reactive protein, MDA and WBC levels was measured and compound muscle action potential (CMAP) distal latans, amplitudes were measured by using ENMG in rats with SICIN.

RESULTS

When untreated sepsis group was compared with both control and sham groups, CMAP amplitudes and latans were significantly lower (P < 000.1). When CLP, CLP+lacosamide 20 mg/kg and CLP+lacosamide 40 mg/kg groups were compared, plasma levels of TNF-alpha and MDA were significantly higher in the untreated CLP group (F = 12.74, P < 0.0001), (F = 19.43, P < 0.05). In the CLP+lacosamide 40 mg/kg group, CRP levels were significantly lower only compared to the CLP group (P < 0.001).

DISCUSSION

We have showed that lacosamide may have beneficial effects on early SICIN by its potential anti-inflammatory and lipid peroxidation inhibiting activities; however, further comprehensive studies are required to clarify these effects.

摘要

目的

危重病性神经病(CIN)是一种可能发生于具有严重全身反应的疾病中的病症,尤其是在脓毒症中。本研究的目的是通过在脓毒症诱导的危重病性神经病(SICIN)大鼠中使用肌电图(ENMG)测量肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、丙二醛(MDA)和白细胞(WBC),来研究拉科酰胺潜在的抗炎和抑制脂质过氧化的活性。

方法

对39只大鼠进行盲肠结扎和穿刺(CLP)手术以诱导脓毒症模型。研究组设计如下:第1组:正常(非手术);第2组:(假手术);第3组:CLP(未治疗组);第4组:CLP加20mg/kg拉科酰胺;第5组:CLP加40mg/kg拉科酰胺。在患有SICIN的大鼠中,使用ENMG测量TNF-α、C反应蛋白、MDA和WBC水平,并测量复合肌肉动作电位(CMAP)的远端潜伏期和波幅。

结果

当将未治疗的脓毒症组与对照组和假手术组进行比较时,CMAP波幅和潜伏期显著更低(P<0.0001)。当比较CLP组、CLP + 20mg/kg拉科酰胺组和CLP + 40mg/kg拉科酰胺组时,未治疗的CLP组中TNF-α和MDA的血浆水平显著更高(F = 12.74,P<0.0001),(F = 19.43, P<0.05)。在CLP + 40mg/kg拉科酰胺组中,仅与CLP组相比,CRP水平显著更低(P<0.001)。

讨论

我们已经表明,拉科酰胺可能因其潜在的抗炎和抑制脂质过氧化活性而对早期SICIN具有有益作用;然而,需要进一步的综合研究来阐明这些作用。

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