中文摘要：

目的: Osteopontin (OPN ) ，多功能的蛋白质，被报导了是在 acetaminophen hepatotoxicity 的 protoxicant。在这研究，在 acetaminophen 毒性位于 OPN 的有害角色下面的机制被探索。

英文摘要：

Aim： Osteopontin （OPN）, a multifunctional protein, has been reported to be protoxicant in acetaminophen hepatotoxicity. In this study, the mechanisms underlying the detrimental role of OPN in acetaminophen toxicity were explored. Methods： Male C57BL/6 （wild-type, WT） and OPN-/-mice were administered with acetaminophen （500 mg/kg, ip）. After the treatment, serum transaminase （ALT）, as well as OPN expression, histology changes, oxidative stress and inflammation response in liver tissue were studied. Freshly isolated hepatocytes of WT and OPN-/- mice were prepared. Results： Acetaminophen administration significantly increased OPN protein level in livers of WT mice. OPN expression was mainly local- ized in hepatic macrophages 6 h after the administration. In OPN-/- mice, acetaminophen-induced serum ALT release was reduced, but the centrilobular hepatic necrosis was increased. In OPN-/- mice, the expression of CYP2E1 and CYPIA2 in livers was significantly increased; GSH depletion and lipid peroxidation in livers were enhanced. On the other hand, OPN-/- mice exhibited less macrophage and neutrophil infiltration and reduced expression of proinflammatory cytokines TNF-a and IL-la in livers. An anti-OPN neutralizing antibody significantly reduced acetaminophen-induced serum ALT level and inflammatory infiltration in livers of WT mice. Conclusion： OPN plays a dual role in acetaminophen toxicity： OPN in hepatocytes inhibits acetaminophen metabolism, while OPN in macrophages enhances acetaminophen toxicity via recruitment of inflammatory cells and production of proinflammatory cytokines.