摘要目的 探讨白介素-1受体拮抗剂(IL-1 Ra)与间充质干细胞(MSCs)移植治疗肝切除后肝功能衰竭的协同效应及机制.方法 巴马小型猪随机分为五组:假手术组;模型对照组:85％肝大部切除术诱导急性肝功能衰竭;IL-1 Ra组:肝切术前6小时耳缘静脉注射IL-1 Ra;MSCs组:肝切除术后24小时门静脉移植8×107 MSCs;联合治疗组:耳缘静脉推注IL-1 Ra,门静脉移植8×107 MSCs.检测各组生化指标、炎症因子、病理改变、生存时间、移植细胞体内分布、肝细胞凋亡与再生情况、AKT及NF-κB表达.结果 MSCs组、IL-1 Ra组、联合组平均存活时间分别为(24.3±4.0)d、(21.7±4.7)d、(35.3±6.7)d;联合组生化指标和炎症因子水平明显改善;MSCs组、IL-1 Ra组、联合组病理学评分分别为5.83 ±0.76、6.67±1.04、3.50 ±0.87.联合组较对照组肝细胞凋亡明显下降(P＜0.05),增殖明显升高(P＜0.05).联合组AKT表达显著升高,NF-κB表达明显降低.结论 MSC联合IL-1 Ra可通过抑制炎症反应和减少凋亡促进肝脏修复和再生,具有协同效应.

abstractsObjective To study the synergetic effect and possible mechanism of transplanting mesenchymal stem cells (MSCs) in combination with interleukin-1 receptor antagonist (IL-1Ra) on acute liver failure (ALF).Methods MSCs transplantation combined with IL-1Ra was used for a swine model of ALF induced by 85％ total hepatectomy.The living conditions,blood samples and survival time were recorded or collected for analysis of hepatic function.Liver injury histology was analyzed.Hepatic cell regeneration and apoptosis were studied by immunohistochemistry staining of Ki67 and TUNELassays respectively.The expression levels of AKT and NF-κB were analyzed by Western blotting.Results The difference on the survival time between the model group and combined therapy group was statistically significant (P ＜ 0.05).Combined therapy displayed improvement not only in the serum biochemical conditions but also in the serum inflammatory cytokines.Furthermore,the observed hepatic histopathological score was significantly less compared to model group.In addition,the combined therapy group significantly inhibited the liver cell apoptosis and increased hepatic cell regeneration.Finally,a significant increase in AKT expression and decrease of NF-κB expression (P ＜ 0.05) were observed,which was consistent with their important roles in liver regeneration.Conclusion The combined therapy displayed a synergistic effect on liver regeneration,by promoting restoration and reconstruction of ALF,through regulation of inflammation and apoptosis signaling network.