脓毒症小鼠血清HMGB1与心肌损伤程度、炎症相关因子、BNP及cTnI水平的关系

目的探讨血清高迁移率族蛋白B1(high mobility group box 1,HMGB1)在脓毒症小鼠心肌损伤中的作用及与心肌细胞炎症因子、血清B型钠尿肽(B-type natriuretic peptide,BNP)和肌钙蛋白(troponin,cTnI)的相关性。方法本研究选取6～8周龄、SPF级的昆明系小鼠60只,采用随机数字表法分为模型组、假手术组各30只,采用小鼠盲肠结扎穿孔法建立脓毒症小鼠模型,观察不同时间点小鼠血清HMGB1的水平变化,探讨其与心肌细胞凋亡率、心肌细胞炎症因子、血清B型钠尿肽(BNP)和肌钙蛋白(cTnI)的相关性。结果在0 h时刻,模型组和假手术组的血清HMGB1水平、心肌细胞凋亡率差异无统计学意义(P>0.05);在造模后12、24、48及72 h,模型组小鼠的血清HMGB1水平、心肌细胞凋亡率显著高于假手术组,差异均有统计学意义(P<0.05);在造模后48 h,模型组心肌组织中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-10、血清BNP、血清cTnI水平显著高于假手术组(P<0.05);在造模后48 h,模型组心肌组织中TNF-α、IL-6、IL-10、血清BNP、血清cTnI水平与血清HMGB1均呈显著正相关(P<0.05)。结论血清HMGB1在脓毒症小鼠中水平升高趋势明显,并且与小鼠心肌损伤具有密切的关系。

Relationship of serum high mobility group box 1 with myocardial injury,inflammatory related factors and changes of B-type natriuretic peptide and troponin in septic mice

Objective To explore the role of serum high mobility group box 1 (HMGB1) in myocardial injury in septic mice and its correlations with myocardial inflammatory factors, serum B-type natriuretic peptide (BNP) and troponin (cTnI). Methods Sixty Kunming mice with 6-8 weeks old and SPF grades were selected in this study, and then the random number table method was used to divide them into the model group and the sham operation group (each n=30). Sepsis models were established by cecal ligation and puncture in mice. The changes of serum HMGB1 levels in mice at different time points were observed, and then its correlations with cardiomyocyte apoptosis rate (CMAR), myocardial inflammatory factors, serum BNP and cTnI were explored. Results No statistically significant differences were found in serum HMGB1 level and CMAR at 0 h between the model group and the sham operation group (both P>0.05). At 12, 24, 48 and 72 hours after the model establishment, serum HMGB1 level and CMAR were significantly higher in the model group than in the sham operation group, with statistically significant differences (both P<0.05). At 48 hours after the model establishment, the levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6), interleukin-10 (IL-10), serum BNP and serum cTnI were significantly higher in the model group than in the sham operation group (all P<0.05). At 48 hours after the model establishment, the levels of TNF-α, IL-6, IL-10, serum BNP and serum cTnI in the myocardial tissue of the model group were significantly positively correlated with serum HMGB1 (all P<0.05). Conclusions Serum HMGB1 level shows a significant increasing tendency in septic mice, and is closely related to myocardial damage in mice.