摘要
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 law of acute liver necrosis induced by tumor necrosis factor (TNF) in mice, and the liver profection by TNF and its mechanism. Methods: Intraperitoneal injection of recombinant human tumor necrosis factor alpha(rhTNF α) and D galactosamine(GalN) elicited acute liver necrosis in Balb/c mice. In another experiment, pretreatment of mice by rhTNF α only was carried out before treatment as above at different interval,and hepatic injury was observed. At last, the effect of rhTNF α on the expression of heat shock protein 70 (HSP70) in mouse liver was studied by Western blot analysis. Results: The severity of hepatic necrosis was dependent on the doses of rhTNF α. The more the rhTNF α injected, the more severity of the liver necrosis. However,overt hepatic injury did not develop in mice in which only rhTNF α was injected and treatment with rhTNF resulted in desensitization of the mice to its lethal effect . Desensitization developed rapidly(0.5 1h) and abated 24 to 48h postinjection. The increased expression of HSP70 was in consistent with the liver profection induced by TNF in mouse liver. Conclusion: TNF can mediate necrotic effect on liver tissues under some conditions and its deleterious effects are dose dependent. On the other hand, TNF can induced liver profection under some conditions. TNF can induce increased expression of HSP70 in mouse liver. The HSP70 may be one important part of the antagonistic mechanism which could protect liver cells from TNF cytotoxicity
出处
《第二军医大学学报》
CAS
CSCD
北大核心
1997年第2期173-176,共4页
Academic Journal of Second Military Medical University
关键词
肿瘤坏死因子
急性
肝坏死
氨基半乳糖
肝脏保护
tumor necrosis factor
acute liver necrosis
D galactosamine
heat shock protein 70
liver profection.
