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肉毒碱对脓毒症大鼠急性肺损伤的保护作用的机制评价。

Mechanistic Evaluation of the Protective Effect of Carnosine on Acute Lung Injury in Sepsis Rats.

机构信息

Department of Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, PR China.

出版信息

Pharmacology. 2017;100(5-6):292-300. doi: 10.1159/000479879. Epub 2017 Aug 25.

DOI:10.1159/000479879
PMID:28848223
Abstract

This study analyzes the sepsis healing therapeutic potential of carnosine against experimentally sepsis-induced male albino rats. Carnosine in 2 different doses, 25 mg/kg and 50 mg/kg, were administered for 30 consecutive days. At the end of the treatment, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and myeloperoxidase activities were measured. Lungs weight and total protein content were determined in the bronchoalveolar fluid (BALF). Cytokines such as macrophage inhibitory factor (MIF), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were determined in the BALF. In addition, the histopathological analysis was also carried out to understand the effect of carnosine in the cellular architecture. Carnosine treatment significantly renormalized the lipid peroxidation and other antioxidant enzymes. IL-β, TNF-α, and MIF were found to be reduced after carnosine treatment. After carnosine treatment, the intensity of sepsis was significantly reduced evidenced by histopathological analysis. In western blot analysis, carnosine treatment causes the upregulation of IκBα together with the downregulation of the expressions of p65 and p-IKKα/β (Ser 180/Ser 181).

摘要

本研究分析了肌肽对实验性脓毒症诱导的雄性白化大鼠的脓毒症愈合治疗潜力。肌肽以 25mg/kg 和 50mg/kg 的 2 种不同剂量连续给药 30 天。治疗结束时,测定脂质过氧化、过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和髓过氧化物酶的活性。测定支气管肺泡灌洗液(BALF)中的肺重和总蛋白含量。测定 BALF 中的巨噬细胞抑制因子(MIF)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)等细胞因子。此外,还进行了组织病理学分析,以了解肌肽对细胞结构的影响。肌肽治疗可显著使脂质过氧化和其他抗氧化酶正常化。IL-β、TNF-α 和 MIF 在肌肽治疗后降低。肌肽治疗后,通过组织病理学分析发现脓毒症的严重程度明显减轻。在 Western blot 分析中,肌肽治疗导致 IκBα 的上调以及 p65 和 p-IKKα/β(Ser180/Ser181)表达的下调。

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