Protection of plasma transfusion against lipopolysaccharide/d-galactosamine-induced fulminant hepatic failure through inhibiting apoptosis of hepatic cells in mice
Protection of plasma transfusion against lipopolysaccharide/d-galactosamine-induced fulminant hepatic failure through inhibiting apoptosis of hepatic cells in mice
复制标题
通过抑制肝细胞凋亡保护血浆输注免受脂多糖/d-半乳糖胺诱导的暴发性肝衰竭
DOI：
10.1631/jzus.b1700277
复制
发表时间：
2018-06-01
影响因子：
5.1
通讯作者：
Wang, Zhen
中科院分区：
文献类型：
--
作者：
Chen, Bing-yu;Jiang, Lu-xi;Wang, Zhen
Fulminant hepatic failure is a severe clinical condition associated with extremely poor outcomes and high mortality. A number of studies have demonstrated the ability of plasma transfusion to successfully treat fulminant hepatic failure, but the underlying mechanisms are not well understood. The aim of the present study is to define the mechanisms of plasma transfusion treatment in lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced mice. LPS/D-GalN treatment in mice causes significant hepatic failure, including increasing serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological changes in centrilobular necrosis and inflammatory cells, and the up-regulation of inflammation (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). When LPS/D-GaIN-induced mice were treated with plasma, these changes were halted. Results showed that plasma transfusion significantly reduced mortality, and decreased the levels of AST, ALT, and inflammation factors such as TNF-α and IL-6. The expression levels of cleaved Caspase-3, BAX, and p53 were down-regulated and Bcl-2 was up-regulated, suggesting that plasma can reduce LPS/D-GalN-induced apoptosis. The protective mechanism of plasma against LPS/D-GalN-induced fulminant hepatic failure is related to the inhibition of the inflammatory response and the reduction in apoptosis through the down-regulation of the p53-induced apoptotic pathway.摘要目的评估血浆输注对脂多糖/D-半乳糖(LPS/D-GalN) 诱导的小鼠急性肝损伤的保护作用,并探讨其作用机制。创新点在小鼠急性肝损伤模型中证明血浆输注对肝损伤的保护作用,且此作用与p53 介导的肝细胞凋亡相关。方法将40 只清洁型ICR 雄性小鼠随机分为4 组 (n=10 每组):(1)对照组;(2)血浆(plamsa) 组;(3)LPS/D-GalN组;(4)LPS/D-GalN+plamsa 组。收集血清和肝组织样本,用天门冬氨酸转氨 酶(AST)和丙氨酸氨基转移酶(ALT)试剂盒 检测血清中AST 和ALT 水平;用酶联免疫吸附 法(ELISA)检测肝组织中白细胞介素-6(IL-6) 和肿瘤坏死因子-α(TNF-α)的表达变化;肝组 织进行苏木精-伊红染色法(HE)和网状纤维染 色,显微镜下观察肝组织病理学变化;用免疫印 迹法(WB)检测凋亡相关蛋白的变化。在腹腔 注射LPS/D-GalN 后 32 小时内对小鼠进行存活分 析。结论LPS/D-GalN 能够显著诱导小鼠的急性肝损伤,包 括增加血清中AST 和ALT 水平;中心小叶坏死 和炎性细胞的组织病理学变化和炎症上调 (TNF-α 和IL-6)。当血浆输注后,这些变化被 缓解。结果显示,血浆输注显著降低小鼠死亡率, 降低AST、ALT 和炎症因子如TNF-α 和IL-6 的 水平。Cleaved Caspase-3、BAX 和p53 的表达下 调,Bcl-2 上调,表明血浆可以减少LPS/D-GalN 诱导的细胞凋亡。血浆输注对LPS/D-GalN 诱导 的急性肝损伤的保护机制与通过p53 诱导的凋亡 途径和炎症因子减少相关。