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目的:观察核转录因子-κB(NF-κB)抑制剂——二硫氨基甲酸酞吡咯烷(PDTC)对内毒素休克大鼠高迁移率族蛋白 B1(HMGB1)mRNA 表达的影响及机制。方法:采用内毒素休克模型,47只大鼠随机分为正常对照组(n=8)、内毒素休克组(n=24)和 PDTC 拮抗组(n=15),留取肝、肺、肾组织检测 HMGB1 mRNA 表达及相应器官功能指标的变化。结果:内毒素攻击可导致动物肝、肺、肾组织 HMGB1 mRNA 表达广泛上调,分别于2～6h 显著增高(P<0.05),12h 呈现进一步升高趋势。PDTC 处理后12h,肝、肺、肾组织 HMGB1 mRNA 表达均显著下调,其中肾组织2～12h 趋于伤前范围;同时,血清丙氨酸转移酶、天冬氨酸转移酶、尿素氮、肌酐水平6h 明显降低(P<0.05),肺组织髓过氧化物酶活性各时相点均显著低于内毒素休克组(P<0.05)。结论:NF-κB抑制剂能显著抑制内毒素休克动物组织 HMGB1 mRNA 的表达,NF-κB信号转导通路参与了内毒素介导 HMGB1基因表达的调控过程,并与脓毒症时多器官功能损害密切相关。
AIM: To investigate the effect and mechanism of nuclear factor-kappa B (NF-κB) inhibitor dithiocarbamate pyrrolidine (PDTC) on high mobility group box 1 protein (HMGB1) mRNA expression in endotoxic shock rats. Methods: Forty-seven rats were randomly divided into normal control group (n = 8), endotoxin shock group (n = 24) and PDTC antagonist group (n = 15) Tissue samples were examined for HMGB1 mRNA expression and corresponding organ function changes. Results: Endotoxin challenge resulted in the up-regulation of HMGB1 mRNA expression in liver, lung and kidney, which were significantly increased from 2 to 6 hours (P <0.05) and further increased at 12 hours. At 12h after PDTC treatment, the expression of HMGB1 mRNA in liver, lung and kidney were significantly down-regulated, and the renal tissue tended to pre-injury within 2 ~ 12h. Serum alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatinine (P <0.05). The levels of myeloperoxidase in lung tissue at each time point were significantly lower than those in endotoxic shock group (P <0.05). Conclusion: NF-κB inhibitor can significantly inhibit the expression of HMGB1 mRNA in endotoxin-shocked animals. NF-κB signal transduction pathway is involved in the regulation of endotoxin-mediated HMGB1 gene expression and is associated with multiple organ dysfunction closely related.