百草枯中毒急性肺损伤的作用机制及丙酮酸乙酯干预研究

目的 探讨高迁移组蛋白B1(HMGB1)/Toll样受体4(TLR-4)在百草枯(PQ)中毒导致急性肺损伤作用机制及丙酮酸乙酯(EP)干预研究.方法 将90只SD大鼠均分为对照组、百草枯中毒组、丙酮酸乙酯治疗组,建立大鼠急性百草枯中毒动物模型后,分别于实验后的6、12、24、48 h、3 d每组随机处死6只大鼠,检测三组大鼠肺组织中肿瘤坏死因子-α(TNF-α)、HMGB1、白细胞介素-1(IL-1)和TLR-4mRNA变化;并测定三组大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)活性变化.结果 与对照组相比,PQ中毒组和EP治疗组染毒后6、12、24、48 h、3 d各时间点,肺组织TNF-α mRNA、HMGB1 mRNA、IL-1 mRNA、TLR-4 mRNA的表达量和丙二醛含量明显升高(均P<0.05),SOD 活力降低(均P<0.05);与PQ中毒组相比,EP治疗组在染毒后12、48 h时间点大鼠肺组织HMGB1 mRNA、TLR-4 mRNA、IL-1 mRNA、TNF-α mRNA表达量及血清MDA含量均降低(均P<0.05),血清SOD 活力均升高(均P<0.05).结论 百草枯中毒急性肺损伤的机制主要与氧化应激、细胞膜脂质过氧化及免疫系统炎症级联放大效应有关,丙酮酸乙酯可通过抑制该过程从而减轻急性肺损伤程度.

Mechanism of acute lung injury induced by paraquat poisoning and the intervention treatment of ethyl pyruvate

Objective To study the mechanism of high mobility group box-1 (HMGB1)/Toll-like receptor 4 (TLR-4) in acute lung injury induced by paraquat poisoning and the intervention treatment of ethyl pyruvate.Methods Ninety SD rats were equally assigned into control group,paraquat poisoning (PQ) group and ethyl pyruvate (EP) treatment group.After establishment of the animal model of acute paraquat poisoning,six rats in each group were sacrificed randomly at 6,12,24,48 h and 3 d,respectively.The expressions of tumor necrosis factor-α (TNF-α),HMGB1,interleukin-1 (IL-1) and TLR-4 mRNA in the lung tissue of three groups were observed,and malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the serum were measured.Results Compared with control group,the expressions of TNF-α mRNA,HMGB1 mRNA,IL-1 mRNA,TLR-4 mRNA and MDA contents in 6,12,24,48 h and 3 d after poisoning in PQ group and EP group were significantly increased (all P<0.05),and the SOD activities were significantly decreased (all P<0.05).Compared with PQ group,the expressions of TNF-α mRNA,HMGB1 mRNA,IL-1 mRNA,TLR-4 mRNA and MDA contents in 24 h and 48 h after poisoning in EP group were significantly decreased (all P<0.05),and the SOD activities were significantly increased (all P<0.05).Conclusions The mechanism of acute lung injury induced by paraquat poisoning was mainly related to oxidative stress,lipid peroxidation of cell membrane and cascade amplification of inflammation reaction,and EP exerted significant protective effect in acute lung injury through inhibiting these pathways.