核转录因子-κappa B在1,2-二氯乙烷中毒所致基质金属蛋白酶-9表达上调过程中的作用

Study on the effect of NF-κB on up-regulation of MMP-9 expression induced by 1,2-dichloroethane poisoning

目的探究核转录因子-κappa B(nuclear transcription factorκappa B,NF-κB)在1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒引起的基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达上调以及脑水肿形成过程中的作用。方法选取40只雌性昆明种小鼠随机分为对照组及3个染毒组。染毒组小鼠置于100 L静式染毒柜中,每天染毒1,2-DCE 1.2 mg/L×3.5 h,分别染毒1 d、2 d和3 d。观察脑组织病理切片,检测各组小鼠的脑含水量、MMP-9以及NF-κB的P65、P50亚基蛋白和mRNA表达水平。结果染毒3 d组的小鼠出现抱抓现象,染毒2 d和3 d组小鼠出现典型脑水肿病理改变,脑含水量、MMP-9以及NF-κB的P65蛋白和mRNA表达水平显著高于对照组(P<0.05)。结论 1,2-DCE可通过诱导小鼠脑组织中NF-κB的活性亚基(P65)表达增强上调MMP-9的表达,从而导致血脑屏障通透性增加,最终引起脑水肿的发生。

To study the effect of nuclear transcription factor kappa B,（NF-κB）on up-regulated expression of matrix metalloproteinase-9 （MMP-9） induced by 1,2-dichloroethane （1,2-DCE） toxic and brain edema. Methods Forty female kunming mice were randomly divided into the control group and three poisoned groups, The mice in poisoned group were poisoned with 1.2 mg/L 1,2-DCE for 3.5 h per day, for up to 1 d, 2 d and 3 d respectively in a 100 L static type canister. Pathological observation of brain tissue was carried out. Brain water content,MMP-9 and NF-κB P65, P50 subunit protein and mRNA expression levels were detected. Results The mice in poison 3 d group underwent brain damage behavior. The pathological changes of typical brain edema were observed in mice in 2 d and 3 d 1,2-DCE poisoning group. Brain water content and P65 and MMP-9 of mice brain at both protein and mRNA level in these two groups were significantly higher than those in control group （P〈0.05）. Conclusion The exposure of 1,2-DCE could increase the expression of active NF-κB subunit （P65） in brain tissue of mice, leading to the up-regulation of MMP-9 expression and subsequent destruction of the blood-brain barrier, eventually leading to brain edema.