Hagiwara Satoshi, Iwasaka Hideo, Uchino Tomoko, Noguchi Takayuki
Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Japan.
Circ J. 2008 Jun;72(6):1012-7. doi: 10.1253/circj.72.1012.
Sepsis can be exacerbated by an inappropriate immune response and the severe impact of this disease on the cardiovascular system is well documented. High mobility group box 1 (HMGB1) protein is an important mediator in the pathogenesis of sepsis and its role in cardiovascular system dysfunction was investigated in an lipopolysaccharide (LPS)-induced rat model of sepsis.
Twelve hours after intravenous bolus injections of LPS (5 mg/kg), rats were killed and heart samples were harvested. Immunoblot analysis was performed to assess expression levels of HMGB1 in cardiac myocytes. Left ventricular developed pressure (LVDP) served as a measure of systolic function. LPS administration was associated with an increase in the expression of HMGB1 in cardiac myocytes and a decrease in cardiac function. Hearts from the LPS-treated rats were also perfused with recombinant HMGB1 and cardiac function measured. The dose-dependent effects observed with elevated HMGB1 included decreased LVDP, decreased left ventricular (LV) + dP/dt(max), decreased absolute value of LV- dP/dt(min), and increased LV end-diastolic pressure.
HMGB1 stimulation produces a negative inotropic effect during septic shock, suggesting an important role for this molecule in cardiovascular system dysfunction during sepsis.
脓毒症可因不适当的免疫反应而加重，且该疾病对心血管系统的严重影响已有充分记录。高迁移率族蛋白B1（HMGB1）是脓毒症发病机制中的重要介质，本研究在脂多糖（LPS）诱导的脓毒症大鼠模型中探讨了其在心血管系统功能障碍中的作用。
静脉推注LPS（5mg/kg）12小时后，处死大鼠并采集心脏样本。进行免疫印迹分析以评估心肌细胞中HMGB1的表达水平。左心室舒张末压（LVDP）作为收缩功能的指标。给予LPS与心肌细胞中HMGB1表达增加及心脏功能降低相关。还用重组HMGB1灌注LPS处理大鼠的心脏并测量心脏功能。观察到HMGB1升高的剂量依赖性效应包括LVDP降低、左心室（LV）+dP/dt（max）降低、LV-dP/dt（min）绝对值降低以及LV舒张末压升高。
HMGB1刺激在脓毒性休克期间产生负性肌力作用，提示该分子在脓毒症期间心血管系统功能障碍中起重要作用。
