NF-κB活化在四氢吡咯二硫代氨基甲酯对抗全氟异丁烯吸入性肺损伤中的预防作用

The role of NF-κB activation in the protective mechanism of pyrrolidine dithiocarbamate against acute lung injury induced by PFIB inhalation in mice

目的 研究四氢吡咯二硫代氨基甲酯 (pyrrolidinedithiocarbamate ,PDTC)对抗小鼠全氟异丁烯(perfluoroisobutylene ,PFIB)吸入性急性肺损伤 (acutelunginjury ,ALI)的预防作用机制。方法 采用小鼠动态吸入PFIB周身暴露染毒装置对实验小鼠进行染毒 ,应用电泳泳动分析法 (electrophoreticmobilityshiftassays ,EMSA)检测肺组织核因子 kappaB (nuclearfactor kappaB ,NF κB)的表达情况 ;采用RIA检测血清中IL 1β、IL 8的含量变化。 结果 PFIB吸入染毒后 ,肺组织内NF κB的表达明显高于正常组 ,染毒前 3 0minPDTC ( 12 0mg/kg)预防可以显著抑制NF κB的表达 ;小鼠血清中IL 1β、IL 8的含量在PFIB染毒后显著升高 ,染毒前 3 0minPDTC ( 12 0mg/kg)预防可以显著地抑制这种升高。结论 PDTC对小鼠PFIB吸入性肺损伤具有预防作用可能是基于其对NF κB的抑制 ,进而抑制前炎症细胞因子IL 1β、IL 8等的过度表达 。

Objective To elucidate a NF-κB activation role in the preventive effect of PDTC against PFIB inhalation induced ALI.To study the intrinsic mechanism of the protective effect of pyrrolidine dithiocarbamate against acute lung injury induced by PFIB inhalation in mice.Method Kunming mice were exposed to gaseous PFIBfor 5 minutes in a flow exposure system.The levels of NF-κB in lung tissue were assayed by EMSA,the levels of IL-1β and IL-8 in serum were measured by RIA.Result Increased activity of NF-κB was observed at 0.5 h after PFIB exposure,overexpression of IL-1β and IL-8,two well known proinflammatory cytokines,was observed at 0.5 h and l h after PFIB inhalation.PDTC(120 mg/kg)pretreatment could significantly inhibit the activation of NF-κB and the overexpression of cytokines,which well related to the preventive effects of PDTC such as decreased mortality,reduced lung coefficient etc..Conclusion The preventative effect of PDTC against the lung injury by PFIB inhalation was identified,the mechanism of action may be its inhibitory effect on the activation of NF-κB.