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目的：研究肿瘤坏死因子（ＴＮＦ）致小鼠肝坏死作用的规律，探讨ＴＮＦ对肝脏保护的诱导作用及机理。方法：应用重组人ＴＮＦα（ｒｈＴＮＦα）对经Ｄ氨基半乳糖（ＧａｌＮ）增敏的雄性ＢＡＬＢ／ｃ小鼠行腹腔注射，诱发急性肝坏死模型。另一实验中，先单独用ｒｈＴＮＦα预处理小鼠，然后在不同时间再予ＧａｌＮ＋ｒｈＴＮＦα，观察小鼠肝损害发生情况。最后，用蛋白免疫印迹检测手段，分析ｒｈＴＮＦα对小鼠肝组织热休克蛋白７０（ＨＳＰ７０）表达的影响。结果：经ＧａｌＮ增敏小鼠，肝损害程度与所用ｒｈＴＮＦα剂量有关。随应用剂量的增加，血清丙氨酸氨基转移酶（ＡＬＴ）渐升高，肝脏病理改变渐重。不经ＧａｌＮ增敏小鼠腹腔注射ｒｈＴＮＦα，无肝损害发生。经ｒｈＴＮＦα预处理的小鼠，在一段时间内可免遭ＧａｌＮ＋ｒｈＴＮＦα的致肝坏死作用。这种保护作用产生于经ｒｈＴＮＦα预处理后０．５～２４ｈ期间。ＴＮＦ诱导肝组织ＨＳＰ７０增量表达与诱生肝脏保护作用有时间上的一致性。结论：ＴＮＦ是小鼠肝坏死的介质；ＴＮＦ诱发小鼠肝坏死是有条件的并呈剂量依赖性。单纯ＴＮＦ，没有致肝坏死作用，一定条件下反可诱导保护。ＴＮＦ可诱导小鼠肝组织ＨＳＰ７０?
Objective: To study the rule of tumor necrosis factor (TNF) -induced hepatic necrosis in mice and to explore the induction of liver protective effect of TNF and its mechanism. Methods: Acute hepatic necrosis was induced by intraperitoneal injection of recombinant human TNFα (rhTNFα) into BALB / c mice which were sensitized with GalN. In another experiment, the mice were pretreated with rhTNF-α alone and then given GalN + rhTNF-α at different times to observe the occurrence of liver damage in mice. Finally, using Western blot detection means, analysis of rhTNF α on the expression of heat shock protein 70 (HSP70) in mouse liver tissue. Results: After GalN sensitized mice, the degree of liver damage was related to the dosage of rhTNFα. Serum alanine aminotransferase (ALT) gradually increased with the increase of applied dose, and the pathological changes of liver increased gradually. Without GalN sensitized mice intraperitoneal injection of rhTNF α, no liver damage occurred. By rhTNF α pretreatment of mice, in a period of time from GalN + rhTNF induced hepatic necrosis. This protective effect produced by rhTNF α pretreatment 0.5 ~ 24h period. TNF-induced liver HSP70 expression induced liver protection consistent with the time. Conclusion: TNF is a mediator of liver necrosis in mice. TNF-induced liver necrosis in mice is conditional and dose-dependent. Simple TNF, did not cause hepatic necrosis, under certain conditions anti-induced protection. TNF can induce mouse liver HSP70?