高迁移率族蛋白1在急性酒精中毒中的作用

急性酒精中毒是一种有害的临床病理状态,短时间内摄入大量的乙醇,会造成多脏器功能损害,通常包括中枢神经抑制、呼吸循环功能障碍、代谢紊乱及免疫系统异常,严重者导致死亡.为了探索急性酒精中毒导致死亡的原因,采用腹腔注射的方法构建了重度急性酒精中毒小鼠模型,发现在模型早期(至迟0.5 h)高迁移率族蛋白1(high mobility group box-1 protein,HMGB1)已显著升高,体外实验也证实酒精导致细胞HMGB1释放,应用单克隆抗体阻断HMGB1有显著的保护作用,这种保护作用是通过降低损伤性炎症反应实现的.在此模型中发现,HMGB1在急性酒精中毒中有着重要的中介作用,调控急性系统性炎症反应,并决定了急性酒精中毒疾病的进程与结局.

HMGB1 Plays a Key Role in Acute Alcoholism

Acute alcoholism is a common pathological state caused by excess intake of ethanol in a short period. It leads to multiple organ functional damage such as central nervous system depression, respiratory and circulatory system dysfunction, metabolism and immune system abnormal. In order to study the reason of death caused by acute alcoholism, we developed a mouse model of acute alcoholism by intraperitoneal injection method. We reported for the first time that HMGB1 played an important role in acute alcoholism. HMGB1 was released and detected in the serum as early as 0.5 h after the intraperitoneal injection of ethanol. Then HMGB1 induced subsequent acute systemic inflammatory response. We further provided evidences indicating that anti-HMGB1 antibody could effectively protect mouse from acute alcohol. This protection was achieved by significantly reducing HMGB1 release and suppressing systemic inflammation.