PM2.5通过上调颗粒酶B促进IL-18表达加重肺部炎症

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。

PM2.5 aggravates lung inflammation by up-regulating granzyme B to promote IL-18 expression

ObjectiveThe 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. MethodsIn 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. ResultsAs 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. ConclusionPM_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.