丙二醇联合肝细胞生长因子修饰牙髓干细胞外泌体保护人表皮细胞的放射损伤  

Radioprotective effect of 1,2-propanediol combined with hepatocyte growth factor-modified dental pulp stem cell exosomes on human skin cells

作　　者：刘云 靳嘉岩 刘玉斌 李强 任博媛 刘赫 吴祖泽 周钢桥 靳继德 Liu Yun;Jin Jiayan;Liu Yubin;Li Qiang;Ren Boyuan;Liu He;Wu Zuze;Zhou Gangqiao;Jin Jide(School of Medicine,Guizhou University,Guiyang 550025,Guizhou Province,China;Beijing Institute of Radiation Medicine,Beijing 100850,China;School of Basic Medical Science,Air Force Medical University,Xi’an 710032,Shaanxi Province,China)

机构地区：[1]贵州大学医学院,贵州省贵阳市550025 [2]军事医学研究院辐射医学研究所,北京市100850 [3]空军军医大学基础医学院,陕西省西安市710032

出　　处：《中国组织工程研究》2024年第13期2002-2008,共7页Chinese Journal of Tissue Engineering Research

基　　金：军队后勤科研课题(AWS21J003),项目分题负责人:靳继德~~。

摘　　要：背景:肿瘤放疗以及核事故等原因引起的放射性皮肤损伤救治仍旧是一个严重的医学问题,单一的防治手段均难以达到有效的治疗结果,寻找新的综合治疗手段是重要的研究方向。目的:观察丙二醇联合肝细胞生长因子修饰牙髓干细胞来源外泌体对于人表皮放射性损伤细胞模型的保护作用及相关作用机制。方法:①使用携带人肝细胞生长因子基因的重组腺病毒感染人牙髓干细胞,超速离心法分离制备外泌体,即Ad.HGF DPSC-Exo。②通过X射线照射诱导人表皮细胞HaCaT放射损伤,细胞分别于照射前用丙二醇预处理,照射后用Ad.HGF DPSC-Exo处理。通过CCK-8法测定细胞增殖活力,流式细胞术检测细胞凋亡情况,细胞划痕实验检测细胞迁移情况,PCR检测P21和P53的表达水平。结果与结论:丙二醇、Ad.HGF.DPSC-Exo、Ad.HGF.DPSC-Exo+丙二醇均可显著改善HaCaT细胞的生长抑制、减少细胞凋亡、提高细胞增殖和迁移能力,显示出较好的辐射防护效果,且Ad.HGF.DPSC-Exo+丙二醇联合作用效果更好。此外,Ad.HGF.DPSC-Exo+丙二醇能够减轻细胞G2/M期阻滞,降低细胞周期调控基因P53和P21的表达。综上所述,丙二醇预处理联合Ad.HGF.DPSC-Exo能够有效保护放射诱导的HaCaT细胞损伤,为辐射性皮肤损伤的防治提供了新的思路和有效方法。BACKGROUND:Skin damage caused by radiation therapy and nuclear accidents is still a serious medical problem.It is difficult to achieve effective treatment results with single prevention and treatment methods.It is an important research direction to find new comprehensive treatment methods.OBJECTIVE:To observe the protective effect and the underlying mechanism of 1,2-propanediol combined with hepatocyte growth factor-modified exosomes derived from dental pulp stem cells on human epidermal radiation damage cell models.METHODS:(1)After infection of human dental pulp stem cells using recombinant adenovirus of human hepatocyte growth factor gene,exosomes,i.e.,Ad.HGF DPSC-Exo,were isolated with ultracentrifugation.(2)HaCat cells were irradiated with X-ray.The cells were treated with 1,2-propanediol before irradiation and Ad.HGF DPSC-Exo after irradiation.Cell proliferative activity was determined by CCK-8 assay.Cell apoptosis was detected by flow cytometry.Cell migration was detected by cell scratch assay.The expression levels of P21 and P53 were detected by PCR.RESULTS AND CONCLUSION:1,2-Propanediol,Ad.HGF.DPSC-Exo,Ad.HGF.DPSC-Exo+1,2-propanediol could significantly improve the growth inhibition of HaCaT cells,reduce cell apoptosis,elevate cell proliferation and migration,and exhibit a good radiation protection effect.Moreover,the combined effect of Ad.HGF.DPSC-Exo+1,2-propanediol was better.Furthermore,Ad.HGF.DPSC-Exo+1,2-propanediol alleviated the cellular G2/M phase block and decreased the expression of cell cycle genes P53 and P21.In conclusion,1,2-propanediol pretreatment combined with Ad.HGF.DPSC-Exo had significant protective effects on radiation-induced HaCaT cell injury and it provided novel ideas and potential methods for the prevention and treatment of radiation-induced skin damage.

关 键 词：放射性皮肤损伤 辐射保护 1 2-丙二醇 干细胞 外泌体 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R751