PROTECTIVE EFFECT OF HIGH-MOBILITY GROUP BOX 1 BLOCKADE ON ACUTE LIVER FAILURE IN RATS
PROTECTIVE EFFECT OF HIGH-MOBILITY GROUP BOX 1 BLOCKADE ON ACUTE LIVER FAILURE IN RATS
复制标题
DOI：
10.1097/shk.0b013e3181df0433
复制
发表时间：
2010-12-01
期刊：
影响因子：
3.1
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
--
作者：
Takano, Kiminori;Shinoda, Masahiro;Kitagawa, Yuko
高迁移率组框1 （HMGB1）是一种单核细胞来源的炎症介质，在休克、组织损伤和内毒素诱导的死亡等情况下释放。本研究通过测定药物性急性肝衰竭（ALF）模型大鼠血浆和肝组织中HMGB1的水平，探讨阻断HMGB1对ALF的影响。成年雄性Sprague-Dawley大鼠，体重250 ~ 300 g。d -半乳糖胺注入阴茎静脉诱导ALF。注射d -半乳糖胺后，连续采集血浆和肝组织样品，测定HMGB1水平。为了检验HMGB1阻断的效果，在注射d -半乳糖胺后立即向阴茎静脉注射抗HMGB1多克隆抗体或对照抗体。ALF诱导后，血浆HMGB1水平升高，肝组织HMGB1水平降低。免疫组化检查显示，ALF动物肝脏HMGB1染色较少，而正常肝脏细胞核染色较强。注射抗HMGB1抗体可显著抑制血浆HMGB1和肝酶，显著抑制血浆炎症因子，显著改善组织学表现，显著提高生存率。注射抗HMGB1抗体组肝脏HMGB1的下降也明显受到抑制。本研究提示，在ALF中，肝脏可能释放HMGB1到血浆中，中和释放的HMGB1对损伤有保护作用。
High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. D-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the D-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of D-galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury.