IL-33 通过氧化应激诱导的炎症加重慢性阻塞性肺疾病的发展。

IL-33 induced inflammation exacerbated the development of chronic obstructive pulmonary disease through oxidative stress.

机构信息

Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Mar;22(6):1758-1764. doi: 10.26355/eurrev_201803_14593.

DOI:10.26355/eurrev_201803_14593

PMID:29630123

Abstract

OBJECTIVE

We aimed at exploring the role of IL-33 in mouse chronic obstructive pulmonary disease and its potential molecular mechanism.

MATERIALS AND METHODS

The chronic obstructive pulmonary disease (COPD) mice model was established by cigarette smoking (CS). COPD mice were randomly assigned into PBS group and IL-33 antibody group. The peripheral blood and lung tissues of mice from two groups were collected for the following experiments. Pathological changes of the lung tissues in both groups were analyzed by hematoxylin and eosin (HE) staining. IL-33 positive cells in lung tissues were detected by immunohistochemistry. Then, the mRNA and protein levels of IL-33, sST2, ERK and TNF-α in the mice peripheral blood of the two groups were accessed by Real-time polymerase chain reaction (RT-PCR) and Western blot. Finally, the indicators related to oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) in the mice serum of two groups were measured.

RESULTS

After successful construction of COPD mouse model by CS, HE staining illustrated that the structure of airway wall of lung tissue in mice from PBS group was irregular. The ciliated columnar epithelium presented significant degeneration, necrosis and shedding. A large amount of inflammation cell infiltration was observed in vascular tissues. The alveolar epithelial structure was severely damaged and alveolar septum was narrowed and ruptured. Adjacent alveoli were found to be fused into larger cysts. The above pathological changes were relatively better in mice from IL-33 antibody group. Immunohistochemical results demonstrated that IL-33 was remarkably deposited in the lung tissue of PBS group. The mRNA and protein levels of IL-33, sST2, ERK and TNF-α in peripheral blood of PBS group were much higher than those of IL-33 antibody group. At the same time, SOD level in PBS group decreased, while MDA level and ROS production increased.

CONCLUSIONS

IL-33 aggravates lung injury in COPD mice by increasing inflammation response and oxidative stress, which may serve as a target for predicting and treating COPD.

摘要

目的

本研究旨在探讨白细胞介素 33（IL-33）在慢性阻塞性肺疾病（COPD）小鼠模型中的作用及其潜在的分子机制。

材料和方法

采用香烟烟雾暴露（CS）方法建立 COPD 小鼠模型。将 COPD 小鼠随机分为 PBS 组和 IL-33 抗体组。收集两组小鼠外周血和肺组织进行以下实验。苏木精-伊红（HE）染色分析两组小鼠肺组织的病理变化。免疫组织化学法检测肺组织中 IL-33 阳性细胞。采用实时聚合酶链反应（RT-PCR）和 Western blot 法检测两组小鼠外周血中 IL-33、可溶性 ST2（sST2）、细胞外信号调节激酶（ERK）和肿瘤坏死因子-α（TNF-α）的 mRNA 和蛋白水平。最后，测量两组小鼠血清中超氧化物歧化酶（SOD）、丙二醛（MDA）和活性氧（ROS）等氧化应激相关指标。

结果

CS 成功构建 COPD 小鼠模型后，HE 染色结果显示，PBS 组小鼠肺组织气道壁结构不规则，纤毛柱状上皮细胞明显变性、坏死、脱落，血管组织内可见大量炎症细胞浸润，肺泡上皮结构严重受损，肺泡间隔变窄、破裂，相邻肺泡融合成较大的囊泡。IL-33 抗体组小鼠的上述病变相对较轻。免疫组化结果显示，PBS 组小鼠肺组织中 IL-33 明显沉积。PBS 组小鼠外周血中 IL-33、sST2、ERK 和 TNF-α 的 mRNA 和蛋白水平均明显高于 IL-33 抗体组。同时，PBS 组 SOD 水平降低，MDA 水平和 ROS 生成增加。