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

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 (rBPI2 1)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 2 0 2± 0 0 97;肺组织 :0 2 6 3± 0 0 91) ,伤后 2 4h则明显增多 (肝组织 :0 487± 0 189;肺组织 :0 5 13± 0 0 6 9,P <0 0 5 ,0 0 1) ,且一直持续至伤后 72h (肝组织 :0 6 87± 0 142 ;肺组织 :0 5 2 0±0 0 76 ,P <0 0 1)。给予rBPI2 1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 0 1)。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 0 5 ,0 0 1)。 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

Objective 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. ]MethodsWistar rats were subjected to a 35% total body surface area full thickness scald injury, and randomly divided into three groups: normal controls (7 rats), thermal injury (24), and recombinant bactericidal/permeability increasing protein (rBPI 21 ) treatment (12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG 1 mRNA expression. Blood samples were obtained 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 thermal injury (liver: 0 687±0 142; lungs: 0 520±0 076, P <0 01). Treatment with rBPI 21 could significantly decrease tissue HMG 1 mRNA expression in 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 and serum GPT, GOT levels, and also between pulmonary HMG 1 mRNA and MPO activities ( P <0 05 0 01). ConclusionsThermal injury per se can markedly enhance HMG 1 gene expression in various organs. Up regulation of HMG 1 expression may be involved in the pathogenesis of endotoxin mediated multiple organ damage secondary to major burns.