ROLE OF LIPOPOLYSACCHARIDE AND TUMOR-NECROSIS-FACTOR-ALPHA IN INDUCTION OF HEPATOCYTE NECROSIS
ROLE OF LIPOPOLYSACCHARIDE AND TUMOR-NECROSIS-FACTOR-ALPHA IN INDUCTION OF HEPATOCYTE NECROSIS
复制标题
DOI：
10.1152/ajpgi.1995.269.2.g297
复制
发表时间：
1995-08-01
影响因子：
4.5
通讯作者：
BOUCHIERHAYES, D
中科院分区：
文献类型：
--
作者：
WANG, JH;REDMOND, HP;BOUCHIERHAYES, D
全身炎症反应综合征(SIRS)时急性肝功能衰竭的发生与肝细胞(HC)的损伤程度和细胞因坏死或凋亡而死亡的程度有关。我们推测，促炎介质如脂多糖和肿瘤坏死因子-α可直接或间接地通过中性粒细胞和枯否细胞的激活而导致HC损伤和细胞死亡，其机制是细胞坏死而不是细胞凋亡。结果表明，内毒素和肿瘤坏死因子α单独或联合作用对培养的大鼠肝细胞具有直接的细胞毒作用，表现为肝细胞酶的释放和肝细胞的坏死。然而，在亚砷酸钠(热休克诱导剂)存在的情况下，内毒素和肿瘤坏死因子-α不能诱导HC凋亡。内毒素或肿瘤坏死因子-α激活的KC和PMN均可引起明显的肝细胞酶释放和HC坏死，其程度与KC和PMN/HC的比例有关。结论：内毒素和肿瘤坏死因子-α可能通过直接或间接诱导肝细胞坏死而不是细胞凋亡，在严重创伤和脓毒症后急性肝功能衰竭的发生发展过程中发挥中心作用。
The occurrence of acute hepatic failure during systemic inflammatory response syndrome (SIRS) is related to the extent of hepatocyte (HC) damage and cell death resulting from necrosis or apoptosis. We hypothesized that proinflammatory mediators such as lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) can, either directly or indirectly through neutrophil (PMN) and Kupffer cell (KC) activation, induce HC damage and cell death, and that the mechanism is cellular necrosis rather than apoptosis. The results in this study demonstrated that LPS and TNF-alpha alone and in combination are directly cytotoxic to cultured rat HC as indicated by the hepatocellular enzyme release and HC necrosis. However, LPS and TNF-alpha, in the presence of sodium arsenite (a heat shock inducer), were unable to induce HC apoptosis. Both KC and PMN activated by either LPS or TNF-alpha induced significant hepatocellular enzyme release and HC necrosis, which was dependent on the ratio of KC and PMN to HC. It is concluded that LPS and TNF-alpha may play a central role in the development of acute hepatic failure after severe trauma and sepsis by directly or indirectly inducing HC necrosis rather than apoptosis.