Goldin R D, Ratnayaka I D, Brown I N, Wickramasinghe S N
Division of Pathology Sciences, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Int J Exp Pathol. 1995 Oct;76(5):353-9.
C57BL/10 mice develop inflammatory and necrotic changes in the liver, as well as raised serum ALT activities, after 9 days of exposure to ethanol vapour. If mice were injected twice with liposomes containing dichloromethylene diphosphonate (DMDP), with an interval of 5 days between the injections, there was complete elimination of Kupffer cells (hepatic macrophages) for a 9-day period starting 1 day after the first injection. The inflammatory and necrotic changes were significantly reduced in mice injected with liposomes containing DMDP as compared to uninjected mice or mice injected with empty liposomes; serum ALT activities were also significantly reduced. No significant difference was seen in serum tumour necrosis factor-alpha levels between the different groups. Kupffer cells therefore play a significant role in the development of the liver damage resulting from exposure to ethanol. Acetaldehyde production by Kupffer cells is one way in which these cells can damage hepatocytes and further work needs to be done to investigate this and other mechanisms.
C57BL/10小鼠在暴露于乙醇蒸气9天后,肝脏会出现炎症和坏死变化,血清谷丙转氨酶(ALT)活性也会升高。如果小鼠分两次注射含有二氯亚甲基二膦酸盐(DMDP)的脂质体,两次注射间隔5天,那么从第一次注射后1天开始的9天时间里,库普弗细胞(肝巨噬细胞)会被完全清除。与未注射或注射空脂质体的小鼠相比,注射含有DMDP脂质体的小鼠的炎症和坏死变化明显减少;血清ALT活性也显著降低。不同组之间血清肿瘤坏死因子-α水平没有显著差异。因此,库普弗细胞在暴露于乙醇导致的肝损伤发展中起重要作用。库普弗细胞产生乙醛是这些细胞损伤肝细胞的一种方式,需要进一步开展研究来探究这一机制及其他机制。