摘要
目的对比PM2.5长时与短时滴注对小鼠肺组织的作用,为急性肺损伤(ALI)模型的构建提供实验依据。方法选取C57BL/6J小鼠作为研究对象,随机分为PM2.5-1 d组、PM2.5-7 d组、PBS-1 d组和PBS-7 d组。PM2.5-1 d组单次气道滴注140 mg(/kg·d)PM2.5悬浮液,PM2.5-7 d组连续7 d气道滴注20 mg(/kg·d)PM2.5悬浮液,构建ALI模型,PBS-1 d组和PBS-7 d组分别以等体积PBS溶液单次或连续滴注作为对照。收集肺泡灌洗液(BALF),检测肺湿/干质量(W/D)比值,观察肺组织病理改变,检测肺组织中炎性因子和肺呼吸功能指标的表达。结果与对应PBS组相比,PM2.5-1 d组和PM2.5-7 d组小鼠肺组织HE染色均出现充血、水肿,肺间质及肺泡腔红细胞渗出、炎性细胞浸润、肺泡壁增厚的现象,且PM2.5-7 d组比PM2.5-1 d组的病理改变更为明显。与对应PBS组相比,PM2.5-1 d组和PM2.5-7 d组BALF总蛋白浓度和W/D比值均升高(P<0.05),且PM2.5-7 d组较PM2.5-1 d组升高更显著(P<0.05)。与对应PBS组相比,PM2.5-1 d组和PM2.5-7 d组TNF-α、CCL2、NLRP3、ACE2和VCAM-1的mRNA表达均升高(P<0.05);与PM2.5-1 d组相比,PM2.5-7 d组TNF-α、CCL2和NLRP3的mRNA表达水平较低(P<0.01),ACE2和VCAM-1的mRNA表达较高(P<0.01)。与PBS-1 d组相比,PM2.5-1 d组IL-6和IL-10的mRNA表达下降(P<0.05);与PBS-7 d组相比,PM2.5-7 d组IL-6和IL-10的mRNA表达升高(P<0.01)。与对应PBS组相比,PM2.5-1 d组和PM2.5-7 d组气道及组织阻力增加(P<0.05),顺应性下降(P<0.05),且PM2.5-7 d组比PM2.5-1 d组的改变更为显著(P<0.05)。结论PM2.5构建的ALI模型中,长时滴注法比短时滴注法所致的肺损伤更严重。
Objective To compare the effects of long-term versus short-term PM2.5 instillation on mouse lung tissue for providing experimental evidence for acute lung injury(ALI)model construction.Methods C57BL/6J mice were selected as study subjects and randomly assigned into four groups:PM2.5-1 d group,PM2.5-7 d group,PBS-1 d group,and PBS-7 d group.The mice in PM2.5-1 d group and PM2.5-7 d group were used to develop ALI models by single tracheal instillation of 140 mg(/kg·d)PM2.5 suspension or con⁃tinuous 7-day tracheal instillation of 20 mg(/kg·d)PM2.5 suspension,respectively.The mice in PBS-1 d group and PBS-7 d group were served as controls and given single or continuous instillation of equal-volume PBS solution.Bronchoalveolar lavage fluid(BALF)was collected to calcuate the wet-to-dry mass ratio(W/D ratio).Histopathological alterations in lung tissue were observed,and the levels of inflammatory factors and pulmonary function parameters were detected.Results Compared with the corresponding PBS groups,HE-stained lung tissue showed congestion,edema,erythrocyte extravasation into the interstitium and alveolar spaces,inflammatorycell infiltration,and thickening of the alveolar septa in PM2.5-1 d group and PM2.5-7 d group,and pathological alterations were more pronounced in PM2.5-7 d group than in PM2.5-1 d group.Compared with the corresponding PBS group,the total protein concentration in BALF and W/D ratio were elevated in PM2.5-1 d group and PM2.5-7 d group(P<0.05),and they were higher in PM2.5-7 d group than in PM2.5-1 d group(P<0.05).Compared with the corresponding PBS group,the mRNA levels of TNF-α,CCL2,NLRP3,ACE2,and VCAM-1 increased significantly(P<0.05).Compared with PM2.5-1 d group,the mRNA levels of TNF-α,CCL2,and NLRP3 decreased in PM2.5-7 d group(P<0.01),while the mRNA levels of ACE2 and VCAM-1 significantly increased(P<0.01).Compared with PBS-1 d group,the mRNA levels of IL-6 and IL-10 decreased in PM2.5-1 d group(P<0.05).Compared with PBS-7 d group,the mRNA levels of IL-6 and IL-10 increased in PM2.5-7 d group(P<0.01).Compared with the corresponding PBS groups,the airway and tissue resistance increased in PM2.5-1 d group and PM2.5-7 d group(P<0.05),and the compliance decreased(P<0.05),and the changes were more pronounced in PM2.5-7 d group than in PM2.5-1 d group(P<0.05).Conclusion The pulmonary injury of ALI model caused by the long-term instillation of PM2.5 is more severe than that induced by the short-term instillation.
作者
徐旋
王鹏镔
马天浩
徐瑶
顾玮
XU Xuan;WANG Pengbin;MA Tianhao;XU Yao;GU Wei(Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment,Bengbu Medical University,Bengbu 233030,China;College of Clinical Medicine,Bengbu Medical University)
出处
《山西医科大学学报》
2026年第2期140-145,共6页
Journal of Shanxi Medical University
基金
安徽省教育厅优秀青年项目(2024AH030040)
安徽省大学生创新训练项目(S202410367155)。
关键词
PM2.5
气道滴注
急性肺损伤
时间效应
模型优化
炎症反应
PM2.5
airway instillation
acute lung injury
temporal effects
model optimization
inflammatory factors
