煤矿粉尘对大鼠白介素-6和let-7e的影响研究

Effects of coal mine dust on interleukin-6 and let-7e in rats

目的 探讨煤矿粉尘致大鼠白介素-6 (IL-6)和let-7e的水平变化,为煤工尘肺机制研究提供依据。方法 清洁级健康雄性SD大鼠64只,随机纳入对照组、煤尘组、混合尘组和石英组。采用非暴露式气管灌注法,对照组一次性给予生理盐水1 mL灌入气管,各染尘组一次性给予粉尘悬浮液1 m L,于染尘1个月和6个月后麻醉处死,取大鼠肺组织进行苏木精-伊红染色,采用Szapiel评分体系进行肺组织病理学评分;采用酶联免疫吸附法检测肺泡灌洗液IL-6水平,实时荧光定量PCR测定let-7e相对表达量。结果 染尘1个月,煤尘组和混合尘组大鼠肺组织内均可见少量煤斑和炎性渗出;石英组大鼠肺组织结构破坏,肺泡间隔轻度纤维化增厚。染尘6个月,煤尘组大鼠可见较多煤斑,肺泡间隔轻度纤维化增厚;混合尘组大鼠肺泡结构破坏,肺间质纤维增生,可见硅结节;石英组大鼠肺泡结构明显破坏,间质纤维增生显著,可见硅结节。染尘时间和染尘类型交互影响肺组织病理学评分、IL-6水平和let-7e相对表达量(P<0.05)。同一染尘类型内,染尘6个月大鼠肺组织病理学评分和IL-6水平高于染尘1个月,let-7e相对表达量低于染尘1个月(均P<0.05);同一染尘时间内,各染尘组大鼠肺组织病理学评分和IL-6水平高于对照组,let-7e相对表达量低于对照组(均P<0.05)。结论 煤矿粉尘可引起大鼠IL-6水平升高和let-7e表达降低,染尘类型与染尘时间可交互影响IL-6和let-7e水平。

Objective To investigate the changes in the levels of interleukin-6(IL-6)and let-7e in rats induced by coal mine dust,so as to provide the basis for the mechanism of coal worker's pneumoconiosis(CWP).Methods Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group,coal dust group,mixed dust group(mixed coal and silica dust)and quartz group.The rats in the control group were exposed to 1 mL physio⁃logical saline by non-exposure tracheal perfusion,and the rats in the dust-exposed groups were exposed to 1 mL dust suspension.Rats were sacrificed by anesthesia after 1 month and 6 months,lung tissue was observed using hematoxylin eosin staining,the pathological change in the lungs was scored using the Szapiel scoring system,the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay,and the expression of let-7e was determined by quantitative real-time PCR.Results A month after exposure,a small amount of coal spots and in⁃flammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group.The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum.Six months after expo⁃sure,there were more coal spots and slightly thickened alveolar septum in the coal dust group,and hyperplasia of pul⁃monary interstitial fibers,destruction of alveolar structure and silica nodules were observed in the mixed dust group.In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and sili⁃ ca nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P< 0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.