感染性休克肝细胞线粒体损伤机制的实验研究

Studies on mechanism of hepatocytic mitochondria damage following septic shock

目的 探讨感染性休克肝细胞线粒体损伤的机制。方法 30只SD大鼠随机分为 3组 ,即假手术组、术后 12h组、术后 16h组。采用盲肠结扎穿孔术 (CLP)制作感染性休克模型 ,比较手术前后肝细胞线粒体呼吸功能和氧化磷酸化功能的变化及线粒体膜ATP酶的活性改变及与大鼠死亡率和血压变化的关系。结果 大鼠在CLP术后 ,随着血压的降低 ,死亡率逐渐增加 ,与之相应肝细胞线粒体Ⅲ态、P/O比值和呼吸控制率 (RCR)明显降低 ,线粒体膜钙 -ATP酶、钠 -钾ATP酶、镁 -ATP酶、钙镁 -ATP酶活性随着病情的发展衰退 ,术后 16h组较 12h组更趋严重 ,与大鼠死亡率上升呈显著正相关。结论 肝细胞线粒体摄氧功能和氧化磷酸化功能减弱 ,膜流动性降低 ,能量代谢功能障碍 ,线粒体内钙镁平衡紊乱是感染性休克肝细胞线粒体损伤的主要机制。

Objective To study mechanism of hepatocytic mitochondria damage following septic shock.Methods 30 SD rats were randomly divided into three groups(artificial group,12 h CLP group,16h CLP group).The model of septic shock was made by cecal ligation and puncture.The liver mitochondria respiratory control ratio(RCR),phosphate/oxygen(P/O) and ATPase activities were assayed.Results In the CLP group,the liver mitochondria respiratory control ratio (RCR),phosphate/oxygen(P/O) and ATPase activities greatly decreased. Compared with 12h CLP group,the 16 h CLP group of RCR,P/O and ATPase activities were significantly reduced,and dead rate gradually increased, which showed obviously positive correlation.Conclusion Liver mitochondria function of ingestion-oxygen and phosphorus-acidification were decreased,membrane fluxion was weakened,energy metablization blocked and inner cell Ca 2+ -Mg 2+ imbalanced. These were the cause of hepatocytic mitochondria damage following septic shock.