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白细胞介素-10与重组人角质形成细胞生长因子-2对大鼠通气诱导性肺损伤的保护作用

Protective effect of interleukin-10 and recombinant human keratinocyte growth factor-2 on ventilation-induced lung injury in rats.

作者信息

Wu J Y, Xiong Z H, Xiong G Z, Ding F Q, Lei J, Lu S, Li Y, He G M, Zhao L L, Liu Z J

机构信息

Department of Intensive Care Unit, Sichuan Cancer Hospital, Chengdu, China.

出版信息

Genet Mol Res. 2015 Dec 2;14(4):15642-51. doi: 10.4238/2015.December.1.16.

Abstract

A rat model of ventilation-induced lung injury (VILI) during anesthesia was generated to investigate the potential role and possible mechanism of interleukin-10 (IL-10) and recombinant human keratinocyte growth factor-2 (rhKGF-2) in protecting anesthetized rats against VILI. A total of 50 male SD rats were randomly divided into 5 groups (N = 10 each): control, VILI, IL-10, rhKGF-2, and IL-10 + rhKGF-2. The VILI (model) group was generated via ventilation, with a tidal volume of 20 mL/kg. Rats in the IL-10 and rhKGF-2 groups received 8 mg/kg IL-10 and 5 mg/kg rhKGF-2, respectively, prior to ventilation. The rats in the IL-10 + rhKGF-2 group received both 8 mg/kg IL-10 and 5 mg/kg rhKGF-2 72 h before ventilation. The total number of nucleated cells and neutrophils in the bronchial alveolar lavage fluid was quantified, and the pathological changes in the pulmonary tissues examined by hematoxylin and eosin staining. The transcript and protein levels of surfactant protein C (SP-C) in lung tissues were detected by real-time polymerase chain reaction and western blot analyses. The SP-C mRNA expression in both IL-10 and rhKGF-2 groups was similar to that in the VILI group. However, this was significantly elevated in the combined treatment group (P < 0.05), indicating that IL-10 and rhKGF-2 could synergistically protect the lung tissue from VILI via the enhancement of SP-C mRNA expression in lung tissues. The protein assay showed a decreased level of infiltration and activation of inflammatory cells, in addition to increased expression of SP-C, thereby confirming the efficacy of this treatment in preventing VILI during anesthesia.

摘要

建立麻醉状态下通气诱导性肺损伤(VILI)大鼠模型,以研究白细胞介素 -10(IL-10)和重组人角质形成细胞生长因子 -2(rhKGF-2)在保护麻醉大鼠免受VILI损伤中的潜在作用及可能机制。将50只雄性SD大鼠随机分为5组(每组N = 10):对照组、VILI组、IL-10组、rhKGF-2组和IL-10 + rhKGF-2组。VILI(模型)组通过通气建立,潮气量为20 mL/kg。IL-10组和rhKGF-2组大鼠在通气前分别给予8 mg/kg IL-10和5 mg/kg rhKGF-2。IL-10 + rhKGF-2组大鼠在通气前72 h给予8 mg/kg IL-10和5 mg/kg rhKGF-2。对支气管肺泡灌洗液中的有核细胞和中性粒细胞总数进行定量,并通过苏木精和伊红染色检查肺组织的病理变化。通过实时聚合酶链反应和蛋白质印迹分析检测肺组织中表面活性蛋白C(SP-C)的转录水平和蛋白水平。IL-10组和rhKGF-2组中SP-C mRNA表达与VILI组相似。然而,联合治疗组中该表达显著升高(P < 0.05),表明IL-10和rhKGF-2可通过增强肺组织中SP-C mRNA表达协同保护肺组织免受VILI损伤。蛋白质检测显示炎症细胞浸润和活化水平降低,同时SP-C表达增加,从而证实该治疗在预防麻醉期间VILI的有效性。

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