Objective To investigate the impact of recombinant human erythropoietin（rhEPO）pretreatment on liver ischemia-reperfusion injury（IRI）in rats and explore the molecular mechanism. Methods Thirty male Sprague-Dawley（SD）rats were randomly divided into three groups equally, including Sham，control and rhEPO groups. Rats in rhEPO group were treated with rhEPO（5 000 U/kg）1 hour before IR induction while sham and control groups were pretreated with saline. 70% liver IR rat model was established in control and rhEPO groups except for sham group. Rat liver tissues and serum were harvested for hematoxylin and eosin（HE）staining，Western Blot，qPCRand enzyme linked immunosorbent assay（ELISA）assay, respectively. Liver histology，transaminases（AST，ALT）， pro-inflammation cytokines（TNF-α，IL-6，IL-1β）and PI3K/AKT signaling were investigated. Results Distinct liver injury was observed with a higher histological damage score and the release of AST and ALT in serum after 70% tissue IR process. rhEPO significantly decreased the pathologic changes of liver and the release of AST and ALT in serum〔AST（U/L）：582.0±52.5 vs. 245.0±31.7 ；ALT（U/L）：388.0±39.6 vs. 166±24.3，both P ＜ 0.05〕. The expression of p-p85 and p-AKT were increased in rhEPO group compared to control group. TNF-α，IL-6 and IL-1β mRNA levels were demonstrated to ascend after IR but lower expression was observed in rhEPO group. Remarkable IRI-induced secretion of TNF-α，IL-6 and IL-1β proteins in serum was verified but rhEPO inhibited the secretion〔TNF-α（pg/ml）：425.0±31.2 vs. 227.0±19.7；IL-6（pg/ml）：353.0±26.4 vs. 189.0±16.3；IL-1β （pg/ml）：511.0±39.6 vs. 328.0±23.2 ，all P ＜ 0.05）〕. Conclusion rhEPO pretreatment can reduce the release of pro-inflammation cytokines and protect liver from IRI in rats through enhanced activation of PI3K/AKT signaling.

目的 探讨重组人促红细胞生成素（rhEPO）对大鼠肝脏缺血 / 再灌注损伤（IRI）的保护作 用和机制。方法 选取健康雄性 Sprague-Dawley（SD）大鼠 30 只，随机均分为实验组（rhEPO 组）、对照 组及假手术组。rhEPO 组术前 1 小时通过尾静脉注射 5 000 U/kg 的 rhEPO，然后建立大鼠 70% 肝脏 IRI 模型。 苏木素 - 伊红（HE）染色观察肝脏组织学变化 ；生化仪测定血清中天冬氨酸转氨酶（AST）和丙氨酸转氨 酶（ALT）的释放量 ；蛋白免疫印迹试验（Western Blot）检测 PI3K/AKT 蛋白磷酸化水平 ；qPCR 测定炎性 细胞因子〔肿瘤坏死因子（TNF-α）、白细胞介素（IL-6 和 IL-1β）〕mRNA 的表达 ；酶联免疫吸附试验 （ELISA）测定血清中 TNF-α、IL-6 和 IL-1β 浓度。结果 对照组有明显的肝组织损伤，血清中 AST 和 ALT 释放量均增加，而 rhEPO 组肝组织损伤程度较轻，转氨酶水平低于对照组〔AST（U/L）：582.0±52.5 比 245.0±31.7 ；ALT（U/L）：388.0±39.6 比 166.0±24.3，均 P ＜ 0.05〕。蛋白检测发现 rhEPO 组 p-p85 和 p-AKT 的表达显著增加，明显高于对照组。qPCR 提示 rhEPO 组炎性因子 TNF-α、IL-6 和 IL-1β mRNA 表达明显低于对照组。ELISA 亦证实 rhEPO 组血清中 TNF-α、IL-6 和 IL-1β 分泌低于对照组〔TNF-α （pg/ml）：425.0±31.2 比 227.0±19.7 ；IL-6（pg/ml）：353.0±26.4 比 189.0±16.3 ；IL-1β（pg/ml）： 511.0±39.6 比 328.0±23.2 ，均 P ＜ 0.05〕。结论 rhEPO 预处理能抑制大鼠肝脏 IRI 时炎性因子释放， 保护肝组织，其机制可能与 PI3K/AKT 信号的进一步活化有关。