PREVENTION OF CARBON TETRACHLORIDE-INDUCED RAT-LIVER INJURY BY SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR
PREVENTION OF CARBON TETRACHLORIDE-INDUCED RAT-LIVER INJURY BY SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR
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DOI：
10.1016/0016-5085(95)90149-3
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发表时间：
1995-06-01
期刊：
影响因子：
29.4
通讯作者：
ALT, E
中科院分区：
文献类型：
--
作者：
CZAJA, MJ;XU, J;ALT, E
背景/目标：大量间接证据表明，细胞因子肿瘤坏死因子a参与了中毒性肝损伤引起的肝细胞损伤。在体内毒性肝损伤模型中测定肿瘤坏死因子a中和对肝细胞损伤的影响。研究方法：通过给予可溶性肿瘤坏死因子受体以中和这种细胞因子的作用，在四氯化碳肝损伤中检查了肿瘤坏死因子a的体内作用。结果如下：可溶性肿瘤坏死因子受体治疗降低了肝损伤的程度，通过降低血清肝酶水平和改善组织学来测量。可溶性肿瘤坏死因子受体的管理也降低了死亡率从60%到16%的致命剂量的四氯化碳。通过组蛋白基因表达时间和损伤后肝脏重量测定，肿瘤坏死因子a中和对肝再生没有不利影响。结论：这些数据为肿瘤坏死因子a在毒素诱导的肝细胞损伤中的作用提供了直接证据。此外，这些研究表明，可溶性肿瘤坏死因子受体治疗可能有利于人类肝脏疾病的治疗。
Background/Aims: Considerable indirect evidence suggests that cytokine tumor necrosis factor a contributes to the hepatocellular damage caused by toxic liver injury. The effects of tumor necrosis factor a neutralization on liver cell injury were determined in an in vivo model of toxic liver injury. Methods: The in vivo effects of tumor necrosis factor a were examined in carbon tetrachloride liver injury through the administration of a soluble tumor necrosis factor receptor to neutralize the effects of this cytokine. Results: Soluble tumor necrosis factor receptor treatment decreased the degree bf liver injury as measured by reduced levels of serum liver enzymes and improved histology. Soluble tumor necrosis factor receptor administration also lowered the mortality from a lethal dose of carbon tetrachloride from 60% to 16%. Tumor necrosis factor a neutralization had no detrimental effect on liver regeneration as determined by the timing of histone gene expression and postinjury liver weight. Conclusions: These data provide direct evidence for a role of tumor necrosis factor a in toxin-induced liver cell injury. In addition, these investigations suggest that soluble tumor necrosis factor receptor therapy may be of benefit in the treatment of human liver disease.