摘要
目的 观察血红素加氧酶-1 (heme oxygenase-1,HO-1)在肺气肿发生发展过程中的保护作用,并探讨其作用机制.方法 选用健康Wistar大鼠建立吸烟所致肺气肿模型.在此期间给予氯化血红素(Hemin)诱导HO-1高表达.模型建立后观察肺组织病理改变,测量平均内衬间隔(MLI)、单位面积平均肺泡数(MAN)和平均肺泡面积(MAA),进行支气管肺泡灌洗液(BALF)细胞分类计数,免疫组化法检测HO-1和IL-17的表达,酶联免疫吸附法(ELISA)检测血清、BALF和肺组织匀浆上清中炎症细胞因子IL-17、IL-8和TNF-α的含量.结果 与对照组比较,烟雾暴露组的病理改变,肺气肿评价指标符合肺气肿的特征,BALF中细胞总数和炎症细胞分类计数数目增多,其中MLI为(34.0 ±2.2)μm,MAN为(2.3±0.5),MAA为(0.5±0.1)μm^2,免疫组化IL-17表达增高,血清、肺组织匀浆上清和BALF中炎症细胞因子含量增多,差异有统计学意义.而Hemin诱导HO-1高表达后可以抑制炎症因子的分泌,减轻吸烟大鼠肺气肿的病变程度.结论 HO-1具有抗炎作用,在一定程度上能够阻止肺气肿的形成.
Objectives The effects of HO-1 on smoke-induced emphysema were tested and the mechanisms were explored in a smoking rat model.Methods In this study,rats were either exposed or sham-exposed to cigarette smoke for emphysema modeling.Hemin were injected during this period to induce HO-1.Subsequently,emphysema development,inflammatory cells and cytokine levels were analyzed.Results Smoke exposure induced emphysema [MLI:(34.0 ± 2.2) μm,MAN:2.3 ± 0.5,MAA:(0.5 ±0.1) μm^2],increased the inflammatory cells count [total number:(41.0 ± 13.9) × 10^4/ml,Neutrophil:(25.0 ± 9.8) × 10^4/ml,Macrophage:(7.2 ± 2.8) ×10^4/ml] and inflammatory cytokine levels especially IL-17 [serum:(33 ± 8.4) pg/ml,lung tissue homogenate:(79 ± 7) pg/ml,BALF:(39 ± 8) pg/ml],IL-8 [serum:(181 ±51) pg/ml,BALF:(162 ±79) pg/ml] and TNF-α[serum:(607 ±85) pg/ml,BALF:(504 ± 223) pg/ml].HO-1 reduced the severity of emphysema [MLI:(28.6 ± 1.1) μm,MAN:(2.7 ±0.7),MAA:(0.4 ±0.1) μm^2];total number:(17.6 ±5.6) × 10^4/ml,Neutrophil:(10.2 ±3.6) × 10^4/ml,Macrophage:(2.6 ± 1.1) × 10^4/ml,suppressed the secretion of IL-17 [serum:(23.9 ± 2.4) pg/ml,lung tissue homogenate:(69.2 ± 3.0) pg/ml,BALF:(17.8 ± 5.3) pg/ml],IL-8 [serum:(103 ± 50) pg/ml,BALF:(114±35) pg/ml] and TNF-α [serum:(423 ±48) pg/ml,BALF:(216 ± 134) pg/ml] and prevented emphysema development.Conclusion HO-1 has anti-inflammatory effects and can prevent smoke-induced emphysema development.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2015年第5期379-383,共5页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
山西省科技厅自然科学基金(2013011055-3)
山西省卫生和计划生育委员会项目(2014039)