慢性PM2.5暴露对C57BL/6J小鼠肺组织炎症和NLRP3炎性小体活性的影响  

Effects of chronic PM2.5 exposure on lung inflammation and NLRP3 inflammasome activation in C57BL/6J mice

作　　者：丁世彬[1,2] 高丽云 李玉春 卜勇军[1] 张国富[1] DING Shibin;GAO Liyun;LI Yuchun;BU Yongjun;ZHANG Guofu(Xinxiang Medical University,Xinxiang 453003,Henan,China;Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine,Xinxiang 453003)

机构地区：[1]新乡医学院,河南新乡453003 [2]河南省分子诊断与检验医学协同创新中心,新乡453003

出　　处：《中国实验动物学报》2019年第4期444-449,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金青年基金(81502843);河南省高等学校重点科研项目(16A330002)~~

摘　　要：目的 研究慢性PM2.5暴露对小鼠肺炎症和NLRP3炎性小体活性的影响,为防治PM2.5所致肺损伤提供新靶点。方法 雄性C57BL/6J小鼠通过不同剂量气管滴注法进行PM2.5染毒,剂量为2,10mg/(kg·bw),对照组小鼠滴注生理盐水。小鼠连续滴注20次,每3d染毒1次后,取血和肺组织。三组小鼠进行血细胞计数;用免疫荧光染色法检测肺组织巨噬细胞水平;用试剂盒测定肺组织中白细胞介素(interleukin,IL)-1β,IL-18水平及caspase-1活性;用实时定量PCR法检测肺组织NLRP3炎性小体相关mRNA表达水平。结果 两个剂量PM2.5染毒均能明显降低单核细胞百分比(P<0.01),增加中性粒白细胞百分比(P<0.01);导致肺炎症发生;增加肺组织caspase-1活性(P<0.01)及NLRP3和ASC的mRNA表达(P<0.01)。与对照组相比,两个剂量组小鼠肺组织IL-1β和IL-18水平均显著增高(P<0.01)。结论 慢性PM2.5暴露可能通过激活肺组织NLRP3炎性小体导致肺炎症发生。Objective To study the effects of chronic PM2.5 exposure on lung inflammation and NLRP3 inflammasome activation in mice,and to provide a new target for prevention and treatment of lung injury caused by PM2.5.Methods Male C57BL/6J mice were exposed to two doses of PM2.5 by tracheal instillation[2,10 mg/(kg.bw)],and the control mice were instilled with normal saline.After mice had been instilled for 20 times(1 time every 3 days),blood and lung tissues were collected.Blood cells were counted,and lung tissue macrophage levels were measured using immunofluorescence staining.Interleukin(IL)-1βand IL-18 levels and caspase-1 activity in lung tissues were determined using ELISA and caspase-1 activity measurement kits.The expression levels of NLRP3 inflammasome-associated mRNA in lung tissue were detected using real-time PCR.Results The two doses of PM2.5 significantly reduced the percentage of monocytes(P<0.01)and induced lung inflammation.The PM2.5-treated mice had a higher percentage of neutrophils(P<0.01),a higher in caspase-1 activity(P<0.01),and a higher in mRNA expression of NLRP3 and ASC(P<0.01)in lung tissues compared with the control mice.IL-1βand IL-18 levels in the lung tissues of the two PM2.5-exposed groups were significantly higher than those seen in the control group(both P<0.01).Conclusion Chronic PM2.5 exposure may induce lung inflammation by activating the NLRP3 inflammasome in the lung tissue.

关 键 词：小鼠 PM2.5 NLRP3炎性小体 肺炎症 

分 类 号：Q95-33[生物学—动物学]