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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2021年06期

页码:

734-740

栏目:

论著

出版日期:

2021-12-20

文章信息/Info

Title:

PM_2.5 aggravates lung inflammation by up-regulating granzyme B to promote IL-18 expression

作者:

王在强¹; 李兰玉²; 傅恩清¹; 韩璐瑶¹; 林红卫¹; 高彦军¹; 张 倩¹; 刘雨柔¹; 金发光¹

710038 西安,空军军医大学第二附属医院呼吸与危重症医学科¹ 200127 上海,上海交通大学附属仁济医院急诊科²

Author(s):

Wang Zaiqiang¹;  Li Lanyu²;  Fu Enqing¹;  Han Luyao¹;  Lin Hongwei¹;  Gao Yanjun¹;  Zhang Qian¹;  Liu Yurou¹;  Jin Faguang¹.

¹Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China; ²Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China

关键词:

颗粒物;  颗粒酶类;  肺部炎症

Keywords:

Particulate Matter;  Granzymes;  Pulmonary inflammation

分类号:

R563

DOI:

10.3877/cma.j.issn.1674-6902.2021.06.006

摘要:

目的 颗粒酶B促进组织炎症的作用日益引起重视,但其在PM_2.5导致的肺部炎症中是否发挥作用还不清楚,本文对在PM_2.5导致的肺部炎症中颗粒酶B的作用进行了研究。方法 第一步构建经气管滴注PM_2.5混悬液诱导大鼠肺部炎症的动物模型,实验分组为PBS组、PM_2.5(2 mg/kg)组、PM_2.5(6 mg/kg)组、PM_2.5(18 mg/kg)组。通过设置PM_2.5滴注剂量梯度,检测不同PM_2.5暴露剂量下大鼠肺组织颗粒酶B表达、病理和炎症评分,以探讨颗粒酶B表达水平与肺部炎症严重程度间有无相关性。第二步通过阻断颗粒酶B,探究在PM_2.5导致的肺部炎症中颗粒酶B是否发挥促进作用。第三步通过阻断IL-18,探究在PM_2.5导致的肺部炎症中颗粒酶B是否通过IL-18发挥作用。结果 随着PM_2.5滴注剂量升高,肺组织颗粒酶B表达增加,肺组织病理切片炎症细胞浸润和肺水肿程度加重,炎症评分增加,PM_2.5促进了肺组织颗粒酶B表达和肺部炎症; 阻断颗粒酶B抑制了IL-18表达和NF-κB磷酸化,改善了PM_2.5导致的肺部炎症; 阻断IL-18抑制了NF-κB磷酸化,改善了PM_2.5导致的肺部炎症。结论 PM_2.5通过上调颗粒酶B促进IL-18表达加重肺部炎症,其机制可能与激活NF-κB信号通路有关。

Abstract:

Objective The role of granzyme B in promoting tissue inflammation has attracted increasing attention, but whether it plays a role in pulmonary inflammation caused by PM_2.5 is still unclear. This study investigated the role of granzyme B in pulmonary inflammation caused by PM_2.5. Methods In the first step, the animal model of rat lung inflammation induced by intratracheal instillation of PM_2.5 suspension was established. The experiment was divided into PBS group, PM_2.5(2 mg/kg)group, PM_2.5(6 mg/kg)group and PM_2.5(18 mg/kg)group. By setting the PM_2.5 instillation dose gradient, we detected the expression of granzyme B, pathology and inflammation scores in rat lung tissues under different PM_2.5 exposure doses to explore whether there is a correlation between the expression level of granzyme B and the severity of lung inflammation. In the second step, whether granzyme B plays a role in promoting pulmonary inflammation caused by PM_2.5 was investigated by blocking granzyme B. In the third step, whether granzyme B acts through IL-18 in PM_2.5-induced pulmonary inflammation was investigated by blocking IL-18. Results As the PM_2.5 instillation dose increased, the expression of granzyme B in lung tissue increased, the degree of inflammatory cell infiltration and pulmonary edema, and the inflammation score in lung tissue pathological sections increased. PM_2.5 increased granzyme B expression and inflammation in the lungs. Blocking granzyme B inhibited IL-18 expression and NF-κB phosphorylation, and reduced lung inflammation caused by PM_2.5. Blocking IL-18 inhibited Phosphorylation of NF-κB and reduced lung inflammation caused by PM_2.5. Conclusion PM_2.5 aggravates lung inflammation by up-regulating granzyme B to promote IL-18 expression, and the mechanism may be related to the activation of NF-κB signaling pathway.

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备注/Memo

备注/Memo:

基金项目: 陕西省重点研发计划(2017ZDL-SF-14-6)
通信作者: 金发光, Email: jinfag@fmmu.edu.cn

常用功能

更新日期/Last Update: 2021-12-20