乌司他丁对百草枯中毒大鼠NF-κB及TNF-α变化的研究  

Study of ulinastatin on the changes of NF-κB and TNF-αin rats with paraquat poisoning

作　　者：张金英[1] 李伟华[1] 郭立莎[1] 王莎莎 李民涛 张志强 ZHANG Jinying;LI Weihua;GUO Lisha;WANG Shasha;LI Mintao;ZHANG Zhiqiang(Department of Emergency,Binzhou Medical University Hospital,Binzhou,Shandong,256603,China)

机构地区：[1]滨州医学院附属医院急诊科,山东滨州256603

出　　处：《临床急诊杂志》2021年第8期549-553,共5页Journal of Clinical Emergency

基　　金：滨州医学院科技计划项目(No:BY2010KJ039)。

摘　　要：目的:观察百草枯中毒大鼠核转录因子κB(NF-κB)活性及肿瘤坏死因子(TNF-α)水平的变化,探讨乌司他丁对百草枯中毒后炎症介质的干预机制。方法:90只清洁级雄性SD大鼠随机等量分为3组(中毒组、干预组和对照组),中毒组和干预组均用百草枯一次性灌胃造模,对照组用等量生理盐水一次性灌胃造模;干预组在造模30 min腹腔内注射乌司他丁,对照组和中毒组在相同时间点腹腔注射等量生理盐水;各组在乌司他丁用药后1 h、4 h、8 h、12 h、24 h、48 h,用NF-κBp65免疫组化试剂盒对肺组织切片并测定NF-κBp65的表达;酶联免疫吸附法(ELISA)测定TNF-α水平的变化;光镜下观察肺组织病理变化。结果:中毒组、干预组肺组织内NF-κBp65活性,TNF-α水平均高于对照组,差异有统计学意义(p<0.05);干预组肺组织内NF-κBp65活性,TNF-α水平低于中毒组,差异有统计学意义(P<0.05);在中毒组和干预组NF-κBp65活性与TNF-α水平的变化存在显著相关性,差异有统计学意义(P<0.05);肺组织病理显示干预组肺损伤情况较中毒组明显减轻。结论:百草枯中毒后早期可激活NF-κB,进而诱导炎症介质合成、释放,促发失控的炎症反应;乌司他丁可抑制NF-κB的活性,减少炎症介质TNF-α的表达,减轻肺损伤。Objective:To observe the changes of nuclear transcription factorκB(NF-κB)activity and tumor necrosis factor(TNF-α)levels in paraquat poisoned rats,and to explore the intervention mechanism of ulinastatin on inflammatory mediators after paraquat poisoning.Methods:Ninty clean male SD rats were randomly divided into 3 groups(poisoning group,intervention group and control group).Rats of both the poisoning group and the intervention group were given paraquat one-time gavage for modeling,and the rats of the control group were given the same amount of normal saline.The rats of intervention group were intraperitoneally injected with ulinastatin 30 minutes after modeling,at the same time equivalent amount of normal saline was injected into the rats of other two groups.Rats were killed at 1 h,4 h,8 h,12 h,24 h and 48 h after taking ulinastatin,blood and pulmonary tissue were collected to determined TNF-α level with ELISA and NF-κBp65 expression with mmunohistochemistry on the pulmonary tissue sections.Results:NF-κBp65 activity and TNF-α level in lung tissues of poisoning group and intervention group were higher than those of control group,and the difference was statistically significant(P<0.05).NF-κBp65 activity and TNF-α level in lung tissue of intervention group were lower in the poisoning group,and the difference was statistically significant(P<0.05).Between the poisoning group and the intervention group,there was a significant correlation between NF-κBp65 activity and TNF-α levels(P<0.05).Lung tissue pathology showed lung injury in the intervention group The situation was significantly ameliorated compared with the poisoned group.Conclusion:NF-κB activation occured in the early stage of paraquat poisoning,which induced the synthesis and release of inflammatory mediators,promoting uncontrolled inflammation.Ulinastatin can inhibit the activity of NF-κB,reduce the expression of inflammatory mediator TNF-α,and improve lung injury.

关 键 词：百草枯 中毒 乌司他丁 核转录因子KB 肿瘤坏死因子 

分 类 号：R631.4[医药卫生—外科学]