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促红细胞生成素对脓毒症大鼠急性肺损伤的保护作用及其相关机制

Protective Effects of Erythropoietin towards Acute Lung Injuries in Rats with Sepsis and Its Related Mechanisms.

作者信息

Zhang Xinliang, Dong Shimin

机构信息

Departments of Emergency and Critical Care Medicine, theThird Hospital of Hebei Medical University, Shijiazhuang, China.

Departments of Emergency and Critical Care Medicine, theThird Hospital of Hebei Medical University, Shijiazhuang, China

出版信息

Ann Clin Lab Sci. 2019 Mar;49(2):257-264.

PMID:31028073
Abstract

The aim of this study was to explore the effects of erythropoietin (EPO) in acute lung injuries in rats with sepsis. 127 male SD rats were divided into 3 groups (n=8): group Sham, group ALI (sepsis-caused lung injury), group EPO (EPO intervention). The blood gas analysis, C-reactive protein level (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 were detected and compared. The water content fraction and myeloperoxidase (MPO) activities, apoptosis, and expression level of nuclear factor -κB (NF-κB p65) in lung tissues were also detected. Compared to group Sham, the oxygenation index of group ALI was decreased (140.66±12.82 vs. 194.7±16.36), CRP (peak value: 2.31±0.33 mg/L vs. 1.00±0.16 mg/L), IL-10 (peak value: 711.26±84.97 ng/L vs. 51.21±11.45 ng/L), TNF-a (63.69±6.85 ng/L vs. 12.92±0.91 ng/L), and IL-6 (peak value: 1768.93±195.11 ng/L vs. 68.71±11.48 ng/L) increased (<0.01), and the lung cell apoptosis and expression of NF-κB p65 (302.75±51.38 vs. 121.46±11.79) were also increased (<0.01), and there was a recovery of EPO group (<0.01). Group ALI exhibited pulmonary interstitial and alveolar edema, hemorrhage, and lung collapse, but the EPO intervention significantly reduced the above lung pathological changes (the water content was 70.36±1.24% in Sham group, 84.26±3.07% in ALI group and 75.72±1.96% in EPO group, <0.01; MPO: 2.23±0.67, 7.56±1.02, 5.73±0.86, <0.01; apoptotic index: 3.73±0.39, 25.69±4.54, 9.59±2.59, <0.01). EPO could inhibit the expression of NF-κB in lung tissues, inhibit the levels of proinflammatory cytokines TNF-a and IL-6, but improve the level of anti-inflammatory cytokine IL-10, thus reducing the pathological changes of lung tissues and producing protective effects towards lung tissues.

摘要

本研究旨在探讨促红细胞生成素(EPO)对脓毒症大鼠急性肺损伤的影响。将127只雄性SD大鼠分为3组(每组n = 8):假手术组、ALI组(脓毒症所致肺损伤组)、EPO组(EPO干预组)。检测并比较血气分析、C反应蛋白水平(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和IL-10。还检测了肺组织中的水分含量分数、髓过氧化物酶(MPO)活性、细胞凋亡以及核因子-κB(NF-κB p65)的表达水平。与假手术组相比,ALI组的氧合指数降低(140.66±12.82 vs. 194.7±16.36),CRP(峰值:2.31±0.33 mg/L vs. 1.00±0.16 mg/L)、IL-10(峰值:711.26±84.97 ng/L vs. 51.21±11.45 ng/L)、TNF-α(63.69±6.85 ng/L vs. 12.92±0.91 ng/L)和IL-6(峰值:1768.93±195.11 ng/L vs. 68.71±11.48 ng/L)升高(P<0.01),肺细胞凋亡及NF-κB p65的表达(302.75±51.38 vs. 121.46±11.79)也升高(P<0.01),而EPO组有恢复(P<0.01)。ALI组出现肺间质和肺泡水肿、出血及肺萎陷,但EPO干预显著减轻了上述肺部病理变化(假手术组水分含量为70.36±1.24%,ALI组为84.26±3.07%,EPO组为75.72±1.96%,P<0.01;MPO:2.23±0.67、7.56±1.02、5.73±0.86,P<0.01;凋亡指数:3.73±0.39、25.69±4.54、9.59±2.59,P<0.01)。EPO可抑制肺组织中NF-κB的表达,抑制促炎细胞因子TNF-α和IL-6的水平,但提高抗炎细胞因子IL-10的水平,从而减轻肺组织的病理变化,对肺组织产生保护作用。

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