HMGB1介导自噬保护肝细胞损伤的机制研究  

HMGB1 mediated autophagy protects the hepatocyte injury in sepsis

作　　者：孙健[1] 徐康[1] 彭耀荣[1] 朱玥[1] 唐启彬[1] 林浩铭[1] 王捷[1] 

机构地区：[1]中山大学孙逸仙纪念医院胆胰外科,广州510120

出　　处：《岭南现代临床外科》2015年第5期538-541,共4页Lingnan Modern Clinics in Surgery

基　　金：广东省自然科学基金(S2013040015308)

摘　　要：目的研究脓毒血症中HMGB1迁移介导自噬保护肝细胞损伤的机制。方法 Lewis雄性大鼠72只根据随机数字表法分为内毒素组(n=18)、自噬诱导组(n=18)、自噬抑制组(n=18)和空白组(n=18),建立内毒素血症的大鼠模型,内毒素组经腹腔给予内毒素(LPS,25 mg/kg)诱导内毒素血症;自噬诱导和抑制组首先分别经腹腔给予雷帕霉素或渥曼青霉素进行预刺激,预刺激1 h后腹腔注射LPS诱导内毒素血症;空白组腹腔注射林格液1 m L;术后6 h、24 h、48 h进行高迁移率族蛋白B1(HMGB1)、自噬、肝脏功能与细胞因子的检测。结果内毒素组肝脏HMGB-1出现转位,术后6 h胞质HMGB1水平显著升高(P<0.01),肝酶及IL-1β水平显著升高,肝脏自噬增加;自噬抑制组较内毒素组术后肝酶、IL-1β水平均显著升高(P<0.01);而自噬诱导组与内毒素组相比,肝酶、IL-1β水平显著降低(P<0.01)。结论脓毒血症HMGB1迁移介导自噬调控IL-1β减轻内毒素血症时的肝细胞损伤,促进肝功能的恢复,在感染致肝细胞损伤中起保护作用。Objective To study the mechanism of high migration rate group protein B1（HMGB1）migration mediated autophagy protects the liver cells injury in sepsis.Methods Seventy-two male Lewis rats were randomly divided into endotoxin group（n =18）,autophagy induction group（n =18）,autophagy inhibition group（n =18）and control group（n =18）.The rats in endotoxin group was given intraperitoneal injection of endotoxin（LPS,25 mg / kg）to induce endotoxemia.Rats in autophagy induction group and inhibition group received intraperitoneal administration of rapamycin or ward penicillin pre stimulation respectively,and followed establishment of endotoxemia one hour later.Rats in blank group were treated with intraperitoneal injection of Ringer＇s solution（1 ml）.The changes of HMGB1 and autophagy in liver tissue,liver function and cytokines were observed on the time points of 6 h,24 h,48 h after operation.Results In the endotoxin group,the autophagy of hepatocytes,the HMGB-1 in hepatocytes cytoplasm,the liver enzymes in serum and IL-1β levels increased significantly（P〈0.01）.However,the level of HMGB1,liver enzymes and IL-1β in the rats of autophagy induction group significantly decreased（P〈0.01）compared with the endotoxin group.Conclusion In the sepsis,HMGB1 migration mediated autophagy regulates in IL-1β to reduce liver cell injury and promote the recovery of liver function.

关 键 词：脓毒血症 HMGB1 自噬调控 肝细胞损伤 NALP3炎性体 

分 类 号：R602[医药卫生—外科学] R631[医药卫生—临床医学]