丙酮酸乙酯对烫伤大鼠肺组织高迁移率族蛋白B1表达和肺损伤的影响  

Effect of ethyl pyruvate on expression of pulmonary high mobility group box-1 protein and acute lung injury in rats with delayed resuscitation after burn injury

作　　者：王彦博[1] 姚咏明[2] 王强[3] 王文江[2] 刘玉峰[1] 

机构地区：[1]第四军医大学西京医院皮肤科,西安710032 [2]解放军总医院第一附属医院全军烧伤研究所,北京100037 [3]解放军总医院第二附属医院普外科,北京100091

出　　处：《第三军医大学学报》2008年第21期1984-1987,共4页Journal of Third Military Medical University

基　　金：国家重点基础研究发展计划(973计划)(2005CB522602);国家自然科学基金(30672178, 30872683)~~

摘　　要：目的观察丙酮酸乙酯(ethyl pyruvate,EP)对烫伤大鼠肺组织高迁移率族蛋白B1(high mobility group box-1protein,HMGB1)表达水平及急性肺损伤的影响。方法采用大鼠30%总体表面积Ⅲ度烫伤延迟复苏模型,78只雄性Wistar大鼠按随机数字表法分为假烫伤组(n=18)、烫伤组(n=30)、EP治疗组(n=30),每组分别在假伤或伤后第8、24、72小时活杀留取肺组织。HMGB1基因/蛋白表达分别采用逆转录聚合酶链反应及蛋白免疫印记法、免疫组化方法检测;髓过氧化物酶(myelope roxidase,MPO)活性采用酶学分光光度法测定;并采用HE染色、光镜下观察肺组织病理改变。结果与假烫伤组比较,烫伤组肺组织HMGB1基因/蛋白表达于伤后8～72h显著增强(P<0.05,P<0.01),同时肺组织MPO活性在8h及24h明显升高(P<0.01),病理学观察见肺组织炎细胞浸润,正常结构破坏,其中以24h改变最重。与烫伤组比较,EP治疗组大鼠肺组织8～72h时间点HMGB1表达显著下调(P<0.05),肺组织MPO活性在8、24h时间点显著下降(P<0.01),EP治疗组8～72h肺组织病理形态损害明显减轻。结论HMGB1作为晚期炎症因子参与了烫伤后肺组织炎症反应的病理过程,EP治疗可明显下调肺组织HMGB1表达,并有助于降低肺组织MPO活性,从而减轻烫伤延迟复苏所致急性肺损伤。Objective To investigate the effect of ethyl pyruvate （EP） on pulmonary high mobility group box-1 protein （HMGB1） expression and acute lung injury in rats with delayed resuscitation after burn injury. Methods Wistar rats were inflicted to 30% full-thickness scald injury followed with delayed resuscitation. Seventy-eight male rats were randomly divided into sham scald group （n = 18 ）, scald group （n =30）, and EP treatment group （n = 30）, and they were sacrificed at 8, 24, and 72 h after scald injury. Lung tissue samples were collected to determine HMGB1 mRNA as well as protein expressions, and pulmonary myeloperoxidase （MPO） activity. HMGB1 mRNA level was semi-quantitatively measured by the reverse transcription polymerase chain reaction （RT-PCR） taking GAPDH as an internal standard, and protein expression of HMGB1 was detected by Western blotting and immunohistochemistry. The pathological changes of lung tissues were observed with light microscopy after HE staining. Results Compared to sham scald controls, both mRNA and protein expressions of HMGB1 were significantly enhanced in the lung at 8 to 72 h after scald injury （ P 〈0.05 or 0.01 ） , meanwhile pulmonary MPO activities were markedly increased at 8 and 24 h after scald （ P 〈 0.01 ）. In addition, many inflammatory cells in pulmonary tissues were observed under light microscope following injury. Treatment with EP markedly down-regulated pulmonary HMGB1 mRNA and protein expressions at 8 to 72 h （P 〈 0.05 or 0.01 ）, and reduced pulmonary MPO activities at 8 and 24 h following scald injury （ P 〈 0.01 ）. The histological morphology of pulmonary lesions was ameliorated after treatment with EP. Conclusion These results suggest that HMGB1 might act as a late mediator in the pathogenesis of postburu acute lung injury. Treatment with EP could obviously inhibit pulmonary HMGB1 expression and reduce MPO activity, thereby prevent the development of acute lung injury induced by major burns with delayed resuscitation.

关 键 词：烫伤 丙酮酸乙酯 高迁移率族蛋白B1 急性肺损伤 

分 类 号：R322.35[医药卫生—人体解剖和组织胚胎学] R644.02[医药卫生—基础医学]