放射性肠损伤常见于核事故及战时的核爆炸，也是临床腹部肿瘤放疗过程中常见的并发症，目前缺乏有效的防治手段。间充质干细胞具有分泌细胞因子、免疫调节、易于外源基因转染等优点，将其应用于放射性肠损伤的临床治疗具有广阔的应用前景。MnSOD在机体抗氧化损伤及抗肿瘤中发挥重要的作用。本课题组已建立过表达MnSOD基因的人间充质干细胞株，发现MnSOD过表达对t-BHP诱导产生的细胞凋亡具有保护作用。MnSOD-MSCs移植可提高放射性肠损伤小鼠的生存率，改善小鼠一般情况及肠组织病理学损伤，减少细胞凋亡的发生。本项目拟研究MnSOD-MSCs对放射性肠损伤保护作用，并重点探讨PI3K/Akt/p53信号通路在MnSOD-MSCs保护肠辐射损伤中的分子调控机制。

Nuclear accidents and terrorism present a serious threat for mass casualty. Accidental or intended radiation exposure leads to radiation-induced intestine injury. However, currently there are no approved medical countermeasures for adiation-induced intestine injury. Developing novel and effective therapeutic treatments for radiation-induced intestinal damage is necessary and important. Mesenchymal stem cells (MSCs) derived from bone marrow, a subpopulation of pluripotent stomal cell that have the ability of self-renewal, proliferate, pluripotency transdifferentiation. MSCs have advantages over other stem cells in that they can be easily isolated from patients or donors, readily expanded ex vivo, and possess immunodulatory and reparative properties. Moreover, MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with vectors containing a therapeutic gene. Thus, the therapeutic potential of MSCs has brought into the spotlights in the clinical treatment of radiation-induced intestine injury. Manganese superoxide dismutase (MnSOD) is an important oxygen free radical scavenger in organisms. MnSOD has an effect to resist oxidative stress and tumor. In previous study, our data showed that overexpressing MnSOD showed protective effects on t-BHP induced apoptosis of MSCs. MnSOD-MSCs infusion extended the survival of mice exposed to 5-Gy abdominal irradiation, accelerated the recovery of radiation-induced intestine structural damage. Furthermore, the transplanted MnSOD-MSCs could colonize in the fractionated small bowel. In this study,we pretend to examine the suppressive effects of MnSOD-MSCs on the proliferation and recovery of radiation-injured IEC-6, and to investigate the regulatory mechanisms of MnSOD-MSCs on the radiation-injured IEC-6.

放射性肠损伤常见于核事故及战时的核爆炸，也是临床腹部肿瘤放疗过程中常见的并发症，目前缺乏有效的防治手段。间充质干细胞具有分泌细胞因子、免疫调节、易于外源基因转染等优点，将其应用于放射性肠损伤的临床治疗具有广阔的应用前景。MnSOD在机体抗氧化损伤及抗肿瘤中发挥重要的作用。本研究建立了放射性肠损伤小鼠的动物模型，构建了稳定高表达MnSOD基因的人间充质干细胞株(MnSOD-MSCs)，同时建立了放射性损伤的细胞模型，进一步深入研究了MnSOD-MSCs对放射性肠损伤细胞模型的增殖、凋亡和氧化应激等方面保护作用。