严重烫伤后高迁移率族蛋白-1基因表达的改变及意义
Changes of high mobility group-1 protein gene expression in rats after thermal injury
摘要目的 观察烫伤后肝、肺组织高迁移率族蛋白-1(HMG-1)mRNA表达的变化规律及其与器官功能损害的关系。 方法 采用大鼠35%Ⅲ度烫伤模型,动物随机分为正常对照组、烫伤组和重组杀菌/通透性增加蛋白(rBPI21)治疗组,留取组织和血标本分别检测组织内毒素含量、HMG-1mRNA表达及器官功能指标。 结果 严重烫伤后早期肝、肺组织HMG-1基因表达改变不明显(正常对照组肝组织:0.202±0.097;肺组织:0.263±0.091),伤后24h则明显增多(肝组织:0.487±0.189;肺组织:0.513±0.069,P<0.05,0.01),且一直持续至伤后72h(肝组织:0.687±0.142;肺组织:0.520±0.076,P<0.01)。给予rBPI21治疗可有效抑制肝和肺中内毒素水平的升高,并显著抑制肝、肺组织HMG-1mRNA水平(P<0.01)。相关分析结果显示,肝组织HMG-1mRNA表达与血清谷丙转氨酶、谷草转氨酶水平、肺组织HMG-1mRNA表达与髓过氧化物酶活性呈显著正相关(P<0.05,0.01)。 结论 严重烫伤后肝、肺组织HMG-1表达显著增多,且持续时间较长,局部组织HMG-1诱生与烧伤后内毒素介导的重要器官功能损害关系密切。
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abstractsObjective To investigate changes in high mobility group-1 protein(HMG-1) gene expression in vital organs, and their potential role in mediating multiple organ damage after burns. Methods Wistar rats were subjected to a 35% to tal body surface area full-thickness scald injury, and randomly divided into th ree groups: normal controls (7 rats), thermal injury (24), and recombinant bactericidal/permeability-increasing protein (rBPI21) treatm ent (12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG-1 mRNA expression. Blood samples were ob tained for measurement of organ function parameters. Results HMG-1 gene expression in tissues was significantly increased at 24 hours postburn (liver: 0.487±0.189; lungs: 0.513±0.069, P<0.05,0.01), and remained markedly elevated up to 72 hours after therma l injury (liver: 0.687±0.142; lungs: 0.520±0.076, P<0.01). Treatmen t with rBPI21 could significantly decrease tissue HMG-1 mRNA expression i n vital organs (liver: 0.687±0.142; lungs: 0.520±0.076, P<0.01). Highly positive correlations were observed between hepatic HMG-1 mRNA a nd serum GPT, GOT levels, and also between pulmonary HMG-1 mRNA and MPO activit ies (P<0.05-0.01). Conclusions Therma l injury per se can markedly enhance HMG-1 gene expression in various organs. U p-regulation of HMG-1 expression may be involved in the pathogenesis of endoto xin-mediated multiple organ damage secondary to major burns.
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