褪黑素对小鼠半乳糖胺肝损伤的保护作用

THE PROTECTIVE EFFECT OF MELATONIN ON GALACTOSAMINE-INDUCED LIVER DAMAGE IN MICE

目的探讨褪黑素对小鼠半乳糖胺肝损伤的保护作用及其机制。方法在给小鼠半乳糖胺（800mg／kg）前12h，每隔6hiP褪黑素10mg／kg。用胶原酶消化法分离并培养小鼠肝细胞后，体外加用褪黑素（10-5～10－11mol／L）和／或半乳糖胺（0．5mmol／L）。以测定丙氨酸氨基转换酶（ALT）、而二醛（MDA）和肝细胞活力作为半乳糖胺肝损伤的指标。结果褪黑素可减轻半乳糖胺所致的肝损伤，使肝匀浆MDA含量明显下降（P＜0．05）。经MT整体处理后分离培养的小鼠肝细胞对半乳糖肤的损伤仍有明显的抵抗作用，表现为细胞内ALT的漏出和MDA的含量明显下降，肝细胞活力上升（P＜0．01）。正常小鼠离体肝细胞在原代培养条件下用褪黑素处理，未出现明显的抗损伤作用。结论褪黑素拮抗半乳糖胺肝毒性的作用可能与其增强肝细胞抗损伤的能力有关。

Aim To investigate the protective effect and mechanism of melatonin(MT) on galactosamine(GalN)-induced liver damage in mice. Methods Mice were treated with MT(10mg/kg)at interval of 6 hours,given ip 12 hr prior to the administration of GaiN (800mg/kg). The preparation of mouse liver cells was achieved by collagenase VI for hepatocytes dispersion,and thenwas cultured with MT (10-5～11mol/L)and /or GalN (0. smmol/L). The ananine aminortansferase (ALT)malonaldehyde (MDA)and cell viability were assayed as an index of GaiN-induced liver damage. Results Administration of GalN produced significantlyhigh level of MDA in the liver homogenates,which could be remarkedly reduced by MT(P<0.05). It was also found that the cultured hepatocytes of mice pretreated with MT in vivo still retained the ability resisting GalN-induced cytotoxicity,as indicated bylower level of ALT release and MDA(P<0. 01),as well as higher cell viability(p<0. 01),but MT treatment in vitro had no protective effect on GalN-induced cytotoxicity. Conclusion MT prevents against the toxitive effect of GaiN on the liver in mice,likely due to its ability to confer the resistance to damage on hepatocytes in mice.