血清高迁移率族蛋白B1与脓毒症小鼠心肌细胞凋亡的相关性研究

Correlation between HMGB1 and myocyte apoptosis in septic mice

目的探讨血清高迁移率族蛋白B1(high mobility group box-1,HMGB1)水平与心肌细胞凋亡率及血清脑钠肽(brain natriupeptide,BNP)的相关性;评价正丁酸钠(sodium butyrate,SB)对脓毒症小鼠心肌凋亡的影响及心功能不全的保护效应。方法采用小鼠盲肠结扎穿孔(cecal ligation and puncture,CLP)建立脓毒症模型。120只小鼠随机分为假手术组(Sham组)、CLP组及SB组,每组40只。用ELISA法检测各组0、12、24、48、72 h血清HMGB1与BNP浓度,用流式细胞仪测定各组0、12、24、48、72 h心肌细胞凋亡率,分别对HMGB1与心肌细胞凋亡率、HMGB1与BNP进行相关性分析。另外,研究正丁酸钠对脓毒症小鼠心肌细胞凋亡率、血清BNP以及120 h生存率的影响。结果血清HMGB1浓度在CLP术后12 h开始升高,并与心肌细胞凋亡率及血清BNP浓度在12、24、48、72 h各时间点均呈显著相关性(P<0.05);正丁酸钠能明显降低心肌细胞凋亡率及血清BNP浓度,并显著改善脓毒症小鼠生存率(P<0.05)。结论 HMGB1可能参与脓毒症小鼠心肌凋亡的过程,并导致心功能不全;应用正丁酸钠干预能减轻心肌凋亡,改善心功能。

Objective To investigate the correlation between serum HMGB1, the myocyte apoptosis rate and serum BNP in septic mice and to probe the effect of sodium butyrate （SB） on myocyte apoptosis and cardiac function. Methods The septic mouse model was developed by cecal ligation puncture（CLP）. 120 mice were randomly divided into three groups of 40 each： sham group, CLP group, and SB group. The serum concentration of HMGB1 and BNP was detected by ELISA at 0,12,24,48,72h separately in each group, and the apoptosis rate of myocytes was measured by flow cytometry at the same time. Both the correlation between HMGB1 and the myocyte apoptosis rate and the correlation between HMGB1 and BNP were studied. Meanwhile, the effect of sodium butyrate treatment on the myocyte apoptosis rate , the serum concentration of BNP and the survival prognosis at 120h was observed. Results The serum concentration of HMGB1 began to elevate after CLP 12h. Positive correlation was found not only between HMGB1 and the myoeyte apoptosis rate, but also between HMGB1 and BNP at 12,24,48,72h （P 〈 0.05 ）. Sodium butyrate decreased the apoptosis rate of myocytes and the concentration of BNP, but increased the survival rate （P 〈 0.05）. Conclusions HMGB1 may be involved in the process of myocardial apoptosis in sepsis, which leads to cardiac dysfunction. Sodium butyrate can reduce myocardial apoptosis in sepsis and ameliorate cardiac dysfunction.