IL-9 通过氧化应激加重慢性阻塞性肺疾病的发展。

IL-9 exacerbates the development of chronic obstructive pulmonary disease through oxidative stress.

机构信息

Department of Pneumology, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8877-8884. doi: 10.26355/eurrev_201812_16656.

DOI:10.26355/eurrev_201812_16656

PMID:30575930

Abstract

OBJECTIVE

To investigate the role of IL-9 in chronic obstructive pulmonary disease (COPD), and to explore its potential mechanism.

MATERIALS AND METHODS

A mouse COPD model was established by exposure to cigarette smoke. COPD mice were then randomly assigned into two groups, including: the PBS group and the IL-9 antibody group. The above two groups were treated with phosphate-buffered saline (PBS) or IL-9 injection, respectively. The histopathological changes in lung tissues of mice were observed by hematoxylin-eosin (H&E) staining. Immunohistochemistry was performed to detect IL-9-positive (IL-9+) cells in lung tissues. Expression levels of IL-9, sIL-9R, STAT3, and p-STAT3 in peripheral blood of mice were determined by quantitative Real time-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot, respectively. In addition, the expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected.

RESULTS

H&E staining results showed that the airway wall structure of COPD mice in the PBS group was irregular. Ciliated columnar epithelium exhibited marked degeneration, necrosis and shedding. Besides, numerous inflammatory cell infiltration, narrowing and rupture of the alveolar septa, and larger cysts fused by adjacent alveoli were observed. H&E staining also indicated that the structure of alveolar epithelium was severely impaired in COPD mice. However, the pathological changes in lung tissues of mice in the IL-9 antibody group were much milder than those of the PBS group. Immunohistochemistry results showed a significant deposition of IL-9+ cells in the lung tissues of the PBS group. Meanwhile, the mRNA and protein levels of IL-9, sIL-9R, and p-STAT3 in the PBS group were also remarkably higher than those of the IL-9 antibody group. In addition, SOD content in the PBS group was significantly decreased, whereas the levels of MDA and ROS were significantly increased than those of the IL-9 antibody group.

CONCLUSIONS

IL-9 activated STAT3 and aggravated lung injury in COPD mice by increasing inflammatory and oxidative stress.

摘要

目的

研究白细胞介素-9（IL-9）在慢性阻塞性肺疾病（COPD）中的作用，并探讨其潜在机制。

材料与方法

采用香烟烟雾暴露法建立小鼠 COPD 模型。将 COPD 小鼠随机分为两组：PBS 组和 IL-9 抗体组。两组分别给予磷酸盐缓冲液（PBS）或 IL-9 注射治疗。通过苏木精-伊红（H&E）染色观察小鼠肺组织的组织病理学变化。采用免疫组织化学法检测肺组织中 IL-9 阳性（IL-9+）细胞。通过实时荧光定量聚合酶链反应（qRT-PCR）、酶联免疫吸附试验（ELISA）和 Western blot 分别检测小鼠外周血中 IL-9、可溶性白细胞介素 9 受体（sIL-9R）、信号转导子和转录激活子 3（STAT3）和磷酸化 STAT3（p-STAT3）的表达水平。此外，还检测了超氧化物歧化酶（SOD）、丙二醛（MDA）和活性氧（ROS）的表达水平。

结果

H&E 染色结果显示，PBS 组 COPD 小鼠的气道壁结构不规则。纤毛柱状上皮明显变性、坏死和脱落。此外，还观察到大量炎性细胞浸润、肺泡间隔狭窄和破裂，以及相邻肺泡融合形成的较大囊肿。H&E 染色还表明，COPD 小鼠的肺泡上皮结构严重受损。然而，IL-9 抗体组小鼠的肺组织病理变化明显轻于 PBS 组。免疫组织化学结果显示，PBS 组肺组织中 IL-9+细胞明显沉积。同时，PBS 组 IL-9、sIL-9R 和 p-STAT3 的 mRNA 和蛋白水平也明显高于 IL-9 抗体组。此外，PBS 组 SOD 含量明显降低，而 MDA 和 ROS 水平明显高于 IL-9 抗体组。