微生物气溶胶与有害气体联合吸入动态暴露动物模型建立及评价

目的 研究建立甲醛((Formaldehyde, FA))与铜绿假单胞菌ATCC15692(Pseudomonas aeruginosa, PAO1)气溶胶联合吸入暴露的大鼠呼吸系统损伤模型。方法 8周龄雄性Wistar大鼠31只(中科院实验动物中心)，体质量(180±10) g，随机分为正常对照组(7只)、(3.4±0.3) mg/m3 FA吸入暴露组(8只)、(0.5～1)×107 cfu/m3 PAO1气溶胶吸入暴露组(8只)、FA联合PAO1气溶胶吸入暴露组(8只)。用HOPE-MED 8050型动态气溶胶暴露舱建立大鼠染毒暴露模型，HE染色法检测肺组织结构损伤，ELISA方法测血清IgM、白介素-1β(interleukin-1 beta, IL-1β)、白介素-8(interleukin-8, IL-8)、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、clara细胞分泌蛋白(clara cell secret protein, CC10)因子分泌水平。发光比色法检测血清SOD活性。结果 组织形态学观察显示，3实验组大鼠肺泡间隔增宽、肺间质水肿、肺组织内炎性细胞侵润，肺组织细胞凋亡数明显增加，以FA与PAO1联合暴露组病理学改变最明显。血清学结果显示，3实验组IgM、 TNF-α、IL-1β、IL-8水平、SOD活性升高，以联合暴露吸入组升高更显著(P0.05)。结论 甲醛与PAO1联合暴露后明显促进大鼠肺组织叠加损伤效应。

Established and Evaluated an Animal Model of Microbial Aerosol and Noxious gas Co-exposure by Respiratory Inhalation

Objective Establish the respiratory system injury model of rat by inhalation formaldehyde combining with microbial aerosol. Method Thirty one wistar rat (180±10 g,8 w) were divided into four groups, separately growth under normal condition (group CO28), exposure under(2.5±0.2)ppm formaldehyde (group FA28), exposure under(1×107)cfu/m3 PAO1 (group PAO), and exposure under (3.4±0.3) mg/m3 formaldehyde combining with PAO1 aerosol (group FA&PAO). The animal morphology injury of lung tissue was observed by HE staining, the apoptosis of lung epithelial cells was observed by Tunnel chromogenic in situ detection. The peripheral blood were collected to examination IgM、IL-1β、IL-8、TNF-α、CC10 concentration and SOD activity. Result Morphological observation showed that the lung tissue of three experimental groups was changed with alveolar septum widened, interstitial edema and inflammatory cell infiltration and the most obvious changes were detected in co-exposure groups. Tunnel tests also showed that more apoptotic cells were detected in the lung epithelium cell in co-exposure groups. In contrast to those of normal control groups, after inhalation of microbial aerosol, rat’s serum IgM、 TNF-α、IL-1β、IL-8 levels increased significantly, with more significantly increasing in co-exposure groups(P0.05). Conclusion Formaldehyde combining with microbial aerosol co-exposure induced synergistic damage of rat lung tissues and destruction the scavenging ability of lung tissue to heterogeneity pollutants.