摘 要: 探究核转录因子-kappa B(nuclear transcription factor kappa 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。 |
关键词: 1,2-二氯乙烷 脑水肿 基质金属蛋白酶-9 核转录因子-kappa B |
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基金项目: 国家自然科学基金(编号:81172644;?81573105) |
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Study on the effect of NF-κB on up-regulation of MMP-9 expression induced by 1,2-dichloroethane poisoning |
Pu Jie*, Wang Lingxiao, Tang Hongge, Jin Xiaoxia, Wang Gaoyang, Zhao Fenghong, Jin Yaping
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Health and Medicine Department, School of Public Health, China Medical University, Shenyang 110122, China
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Abstract: 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. |
Keywords: 1,2-DCE brain edema MMP-9 NF-κB |