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环状六肽AcF可减轻大鼠脓毒症诱导的急性肺损伤及死亡率。

The cyclic hexapeptide AcF attenuates sepsis-induced acute lung injury and mortality in rats.

作者信息

Dong H, Shan F, Sun Q, Yang B-X, Li C-P

机构信息

Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Eur Rev Med Pharmacol Sci. 2014;18(18):2727-35.

PMID:25317810
Abstract

OBJECTIVE

The purpose of this study was to elucidate the possible beneficial effects of AcF on acute lung injury (ALI) in a rat model of sepsis.

MATERIALS AND METHODS

Male Sprague-Dawley rats were randomly divided into the following four experimental groups (n = 10 per group): animals undergoing a sham cecal ligature puncture (CLP) (Sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with saline (Saline group) and animals undergoing CLP and treated with AcF (AcF group). At 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight ratio, Protein concentration and the count of inflammatory cells or neutrophils in the BALF were determined. The pathologic changes in lungs were examined with the optical microscopy. Myeloperoxidase (MPO) activity, the expression of inflammatory cytokines were measured in lung tissue and BALF respectively. Survival rates were recorded at 120h in the four groups in another experiment.

RESULTS

Histology findings revealed acute lung injury in rats in the CLP group, whereas those in the AcF-treated group had mild lung injury. Treatment with AcF significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung wet/dry ration, protein concentration and the infiltration of inflammatory cells and neutrophils in the lung tissues. In addition, the secretion of inflammatory cytokines, such as TNF-α, IL-6, IL-1b and macrophage inflammatory protein-2 (MIP-2) was decreased in AcF treated group compared with the control saline treated group.

CONCLUSIONS

AcF administration ameliorates acute lung injury in a rat model of sepsis induced by CLP. AcF can be developed as a novel treatment for severe sepsis-induced ALI.

摘要

目的

本研究旨在阐明乙酰半胱氨酸(AcF)对脓毒症大鼠模型急性肺损伤(ALI)可能的有益作用。

材料与方法

雄性Sprague-Dawley大鼠随机分为以下四个实验组(每组n = 10):接受假盲肠结扎穿刺(CLP)的动物(假手术组);接受CLP的动物(对照组);接受CLP并给予生理盐水治疗的动物(生理盐水组);接受CLP并给予AcF治疗的动物(AcF组)。CLP术后24小时,收集血液、支气管肺泡灌洗液(BALF)和肺组织。测定肺湿/干重比、蛋白质浓度以及BALF中炎性细胞或中性粒细胞计数。用光学显微镜检查肺组织的病理变化。分别测定肺组织和BALF中的髓过氧化物酶(MPO)活性、炎性细胞因子表达。在另一项实验中记录四组动物120小时的生存率。

结果

组织学检查发现CLP组大鼠出现急性肺损伤,而AcF治疗组大鼠肺损伤较轻。AcF治疗显著减轻了CLP诱导的肺水肿和炎症,因为它显著降低了肺湿/干比、蛋白质浓度以及肺组织中炎性细胞和中性粒细胞的浸润。此外,与生理盐水对照组相比,AcF治疗组炎性细胞因子如肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和巨噬细胞炎性蛋白-2(MIP-2)的分泌减少。

结论

给予AcF可改善CLP诱导的脓毒症大鼠模型中的急性肺损伤。AcF可开发为治疗严重脓毒症诱导的ALI的新型药物。

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