摘要
目的探讨氟乙酰胺诱导大鼠急性肺损伤的分子作用机制。方法将40只健康成年SPF级SD大鼠按照体重随机分成4组,分别为对照(去离子水)组和4.0、6.0、9.0 mg/kg氟乙酰胺染毒组,每组10只,雌雄各半。采用一次性灌胃方式进行染毒,染毒容量为20 ml/kg。24 h后,进行肺损伤评分,测定动脉氧分压(PaO2)以及肺组织miR-223、TLR4、NF-κBp65mRNA和TLR4、NF-κBp65、IL-2、TNF-α蛋白的表达水平。结果与对照组比较,各剂量氟乙酰胺染毒组大鼠肺损伤评分升高,而PaO2水平降低,差异均有统计学意义(P<0.05);且随着氟乙酰胺染毒剂量的升高,大鼠肺损伤评分呈上升趋势,而PaO2水平呈下降趋势。与对照组比较,各剂量氟乙酰胺染毒组大鼠肺组织miR-223、TLR4、NF-κBp65 mRNA和TLR4、NF-κBp65、IL-2、TNF-α蛋白的表达水平升高,差异均有统计学意义(P<0.05);且随着氟乙酰胺染毒剂量的升高,大鼠肺组织miR-223、TLR4、NF-κBp65 mRNA和TLR4、NF-κBp65、IL-2、TNF-α蛋白的表达水平均呈上升趋势。结论氟乙酰胺可诱导大鼠急性肺部炎症反应,其机制与氟乙酰胺上调miR-223表达和激活TLR4-NF-κB炎症信号通路有关。
Objective To explore the molecular mechanism of fluoroacetamide-induced acute lung injury in rats.Methods Forty healthy adult SPF grade SD rats were randomly divided into four groups according to body weight,control group and4.0,6.0 and 9.0 mg/kg fluoroacetamide exposure groups,10 rats in each group,half male and half female.The exposure groups were given fluoroacetamide through gavage at 20 ml/kg once.After 24 h-exposure,lung injury was scored the arterial pressure of oxygen(PaO2)and the expression levels of miR-223,TLR4,NF-κBp65 mRNA and TLR4,NF-κBp65,IL-2 and TNF-αprotein in lung tissue were determined.Results Compared with the control group,the lung injury scores of the fluoroacetamidetreated groups were increased,while the PaO2 levels were decreased,the difference was statistically significant(P<0.05).With the increase of the dose of fluoroacetamide,the lung injury score of rats showed an upward trend,while the level of PaO2 showed a downward trend.Compared with the control group,the expression levels of miR-223,TLR4,NF-κBp65 mRNA and TLR4,NF-κBp65,IL-2 and TNF-αprotein in lung tissue of rats exposed to fluacetamide increased significantly(P<0.05);With the increase of fluoroacetamide exposure,the expression of miR-223,TLR4,NF-κBp65 mRNA and TLR4,NF-κBp65,IL-2 and TNF-αprotein in rat lung tissue increased.Conclusion Oral exposure to fluoroacetamide may induce acute lung inflammation in rats,and its mechanism is related to the up-regulation of miR-223 expression and activation of TLR4-NF-κB inflammatory signaling pathway.
作者
郑冲
张人华
赵大志
刘利亚
刘佳
林野
ZHENG Chong;ZHANG Ren-liua;ZHAO Da-zhi;LIU Li-ya;LIU Jia;LIN Ye(Department of Toxicology,Guizhou Prmincial Center for Disease Control and Prevention,Guiyang,Guizhou 550004,China;不详)
出处
《环境与健康杂志》
CAS
北大核心
2019年第9期768-772,F0002,共6页
Journal of Environment and Health
基金
贵州省卫生计生委科学技术基金(gzwjk2017-1-085)。
