Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Jiangsu Province Key Medical Center for Hepatobiliary Disease, Nanjing, China.
Arch Med Res. 2013 Jul;44(5):370-9. doi: 10.1016/j.arcmed.2013.06.004. Epub 2013 Jul 31.
To investigate the synergistic effect of IL-1Ra administration and stem cell transplantation in swine suffering from acute liver failure (ALF), to elucidate the mechanism of IL-1Ra activity and to demonstrate mesenchymal stem cell (MSC) transplantation as a potential treatment for ALF.
Thirty-five Chinese experimental mini-swine were divided into five groups randomly. Group A (n = 7) is the control group and all swine were injected with saline via portal veins. Group B (n = 7) received IL-1Ra via ear veins 6 h before receiving saline. Group C (n = 7) received MSC transplantation and all swine were injected with 8 × 10⁷ MSCs via portal veins. Group D (n = 7) swine were treated with a combination of IL-1Ra and MSC transplantation E (n = 7) also received a combined treatment of both IL-1Ra and bone marrow (BM-MSC) transplantation, except that the IL-1Ra was in the form of chitosan nanoparticles. Liver function, level of cytokines and liver pathological changes were measured in the following 4 weeks.
IL-1Ra chitosan nanoparticles exhibited controlled-release ability in PBS. Swine in Group E showed a significant improvement in inflammation environment, liver function and hepatocyte proliferation. Levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in Group E were elevated compared to other groups.
IL-1Ra chitosan nanoparticles showed significant liver targeting ability and controlled-release characteristics. Combined therapy with IL-1Ra chitosan nanoparticles and MCS transplantation exhibits great synergistic effects through paracrine function and suppression of inflammation.
研究白细胞介素-1 受体拮抗剂（IL-1Ra）给药和干细胞移植对急性肝衰竭（ALF）猪的协同作用，阐明 IL-1Ra 活性的机制，并证明间充质干细胞（MSC）移植作为 ALF 的潜在治疗方法。
35 头中国实验小型猪随机分为五组。A 组（n = 7）为对照组，所有猪均经门静脉注射生理盐水。B 组（n = 7）于接受生理盐水前 6 小时经耳静脉给予 IL-1Ra。C 组（n = 7）接受 MSC 移植，所有猪均经门静脉注射 8 × 10⁷ MSC。D 组（n = 7）猪接受 IL-1Ra 和 MSC 联合移植治疗，E 组（n = 7）也接受 IL-1Ra 和骨髓（BM-MSC）联合移植治疗，不同之处在于 IL-1Ra 为壳聚糖纳米粒形式。在接下来的 4 周内测量肝功能、细胞因子水平和肝组织病理学变化。
IL-1Ra 壳聚糖纳米粒在 PBS 中表现出控释能力。E 组猪的炎症环境、肝功能和肝细胞增殖均显著改善。E 组肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）水平较其他组升高。
IL-1Ra 壳聚糖纳米粒具有明显的肝靶向能力和控释特性。IL-1Ra 壳聚糖纳米粒与 MSC 联合移植通过旁分泌功能和抑制炎症显示出巨大的协同作用。
