建立5-Fu肝损伤小鼠模型，给药后检测外周血白细胞(WBC)数、骨髓有核细胞(BMNC)数及脏器指数，血清ALT和AST活性；肝组织病理切片观察CMP对小鼠肝组织的影响；Western Blot检测肝组织中Keap1、Nrf2、GCL、NF-κB、p38、pp38、Bax和Bcl-2蛋白的表达，免疫组化检测NF-κB和pp38表达。结果表明，与正常组相比，5-Fu导致小鼠肝、脾指数、ALT和AST活性分别升高13.75%、53.76%、39.48%和62.81%；WBC和BMNC数分别降低7.15%和50.81%；肝组织中NF-κB、pp38、Bax表达明显增加，Bcl-2则下降，表明肝损伤模型成功建立。CMP使肝损伤小鼠的肝、脾指数、ALT和AST活性分别下降了12.40%、31.45%、20.83%和20.14%；WBC和BMNC数分别增加了7.47%和18.95%；还明显增加Bcl-2水平,降低NF-κB、pp38和Bax表达。CMP对正常小鼠肝脏无明显作用，但能明显减轻5-Fu毒性，并对肝损伤有明显保护作用，其机制与调控NF-κB、p38MAPK及Bcl-2信号通路有关。

A mouse model of 5-Fu-induced liver injury was established, and peripheral-blood white blood cells (WBC), bone marrow nucleated cells (BMNC), visceral indexes, and alanine transaminase (ALT) and aspartate aminotransferase (AST) activities in serum were quantified after the drug was administered. The effects of CMP on mouse liver tissues were examined using histopathological sectioning of the liver tissues; protein expression levels of Keap1, Nrf2, GCL, NF-κB, p38, pp38, Bax, and Bcl-2 in liver tissues were measured by western blotting; and protein expression levels of NF-κB and pp38 were analyzed by immunohistochemistry. The results showed that compared with the normal group, 5-Fu increased the liver index, spleen index, ALT activity, and AST activity by 13.75%, 53.76%, 39.48%, and 62.81%, respectively. WBC and BMNC values were decreased by 7.15% and 50.81%, respectively; the expression levels of NF-κB, pp38, and Bax in liver tissues were significantly increased, but the expression level of Bcl-2 was decreased, indicating that the liver injury model was successfully established. The CMP treatment of this model decreased the liver index, spleen index, ALT activity, and AST activity by 12.40%, 31.45%, 20.83%, and 20.14%, respectively. WBC and BMNC values were increased by 17.12% and 46.77%, respectively. The expression level of Bcl-2 was significantly increased, while the expression levels of NF-κB, pp38, and Bax were reduced. CMP alone had no significant effect on the liver of normal mice, but effectively reduced the toxicity of 5-Fu and showed apparent hepatoprotective effects. The underlying mechanism is related to the regulation of NF-κB, p38 MAPK, and Bcl-2 signaling pathways.

国家科技部“重大新药创制”科技重大专项课题(2012ZX09501001-004)；国家科技部“重大新药创制”科技重大专项（2012ZX09301-002-001-026)