休克期切痂对烫伤大鼠高迁移率族蛋白B1及多器官损害的影响

Effect of escharectomy during shock stage on plasma high mobility group box protein 1 levels and multiple organ dysfunction in burned rats

目的观察烫伤大鼠循环高迁移率族蛋白B1(HMGB1)变化规律,探讨休克期切痂改善脏器功能的机制.方法 Wistar大鼠30%Ⅲ度烫伤后随机分为24h切痂组和72h切痂组.免疫印迹法、酶生化法检测血浆HMGB1含量及脏器功能指标.结果烫伤后血浆HMGB1水平升高2～4倍(P<0.05或P<0.01),心、肺、肝、肾、肠及脾脏等功能指标明显异常(P<0.05或P<0.01).24h切痂组动物伤后2天血浆HMGB1水平明显下降,同时多脏器功能显著改善(P<0.05);而72h切痂组仅伤后8天血浆HMGB1水平明显降低和脏器功能的改善(P<0.05).血浆HMGB1浓度与肺组织MPO及血浆CK-MB、AST、ALT酶活性以及BUN呈正相关(P<0.01),而与脾淋巴细胞MTT及肠组织DAO呈负相关(P<0.01).结论循环HMGB1可能参与了烫伤后全身多脏器损伤,休克期切痂有助于减少HMGB1的产生.

Objective To mvestigate the changes in plasma high mobility group box protein 1 （HMGB1） levels, and to determine variables pertaining to multiple organs in order to elucidate the potential mechanism underlying beneficial effects of escharectomy during shock stage after severe bums. Methods Wistar rats inflicted with 30% full-thickness thermal injury were randomly divided into thermal injury group, 24h escharectomy group and 72 h escharectomy group, in which escharectomy was performed at 24h and 72h postburn, respectively. Levels of plasma HMGB1 and parameters reflecting organ functions were determined. Results Thermal injury resulted in an increase in plasma HMGB1 levels by 2-to 4-fold （P〈0.05 or P〈0.01）, accompanied by significant deterioration of functional indices of the heart, lung, liver, kidney, intestine, and spleen （P〈0.05 or P〈0.01）. However, HMGB1 levels were markedly reduced （P〈0.05）, and organ functional indices were significantly ameliorated in animals of 24h escharectomy group on postbum day 2, and on the other hand, these findings were not found in those of 72 h escharectomy group until postburn day 8. Moreover, there were significant positive correlations between plasma HMGB1 levels and pulmonary MPO, plasma CK-MB, AST, ALT, as well as BUN contents （P〈0.01）, and negative correlation between plasma HMGB1 and splenocytes proliferative response to Con A, and also intestinal DAO activity （P〈0.01）. Conclusions HMGB1 release might play a role in the development of multiple organ dysfunction, and escharectomy during bum shock stage could reduce the plasma HMGB1 levels and ameliorate multiple organ damage following severe bums.