三子黄石方对骨髓增生异常综合征小鼠细胞自噬作用及其表观遗传学调控机制  

Effects of Sanzi Huangshi Formula on autophagy in mice with myelodysplastic syndrome and its epigenetic regulation mechanism

作　　者：王冬琴[1] 陶雨晨 任建业 胡可心 徐皓 王艳璐 薛婷婷 董孝杰 陆嘉惠[1] WANG Dongqin;TAO Yuchen;REN Jianye;HU Kexin;XU Hao;WANG Yanlu;XUE Tingting;DONG Xiaojie;LU Jiahui(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院,上海200071

出　　处：《中华中医药杂志》2023年第11期5454-5458,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81873286);上海市优秀学术带头人计划(No.20XD1403500);上海市卫生系统优秀人才培养计划项目(No.2018BR15);上海市科学技术委员会医学创新研究专项重大项目(No.21Y31920400);上海申康医院发展中心临床科技创新项目(No.SHDC12020128)。

摘　　要：目的:探讨三子黄石方对骨髓增生异常综合征(MDS)的可能作用机制。方法:15只MDS模型小鼠分为模型组、雄黄组、三子黄石方组,每组5只;另取5只C57BL/6J小鼠作为空白组。经口灌胃给药,2周后采集小鼠骨髓单个核细胞(BMMNCs)标本,使用WesternBlot、ELISA检测自噬蛋白LC3Ⅱ/Ⅰ、组蛋白H4K16ac、H4K16ac转移酶hMOF水平;流式细胞术、共聚焦显微镜检测自噬水平。结果:与空白组比较,模型组hMOF、LC3Ⅱ/Ⅰ蛋白表达及H4K16ac蛋白(量)表达显著降低(P<0.01,P<0.05),自噬水平及囊泡数目显著降低(P<0.01)。与模型组比较,雄黄组、三子黄石方组hMOF、LC3Ⅱ/Ⅰ蛋白表达及H4K16ac蛋白(量)表达显著升高(P<0.05,P<0.01),自噬水平及囊泡数目显著升高(P<0.05,P<0.01)。结论:表观遗传H4K16ac、hMOF表达及自噬降低参与MDS发病。雄黄及三子黄石方可能具有类hMOF/H4K16ac干预作用诱导MDS小鼠BMMNCs自噬发挥抗肿瘤作用,但雄黄组、三子黄石方组尚未发现明显差异。Objective:To explore the possible mechanism of Sanzi Huangshi Formula on myelodysplastic syndrome(MDS).Methods:Fifteen MDS model mice were divided into model group realgar group and Sanzi Huangshi Formula group,with 5 mice in each group;five C57BL/6J mice selected were as blank group.With administration by the way of oral gavage,after 2 weeks later,samples from mice bone marrow mononuclear cells(BMMNCs)were collected to detect the autophagy protein LC3Ⅱ/Ⅰ,H4K16ac and its transferase hMOF via Western Blot and ELISA.Flow cytometry and confocal microscopy was used to detect autophagy levels.Results:Compared with the blank group,the expression of hMOF,LC3Ⅱ/Ⅰand H4K16ac in model group were significantly lower(P<0.01,P<0.05),the autophagy level and number of vesicles were significantly lower(P<0.01).Compared with the model group,the expression of hMOF,LC3Ⅱ/Ⅰand H4K16ac in realgar group and Sanzi Huangshi Formula group were significantly higher(P<0.05,P<0.01),the autophagy level and number of vesicles were significantly higher(P<0.05,P<0.01).Conclusion:The low expression of epigenetic contents such as H4K16ac and hMOF,and autophagy reduction was involved in the pathogenesis of MDS.Realgar and Sanzi Huangshi Formula may exert similarly hMOF/H4K16ac intervention effect in inducing BMMNCs autophagy to fight against tumors in MDS mice.Unfortunately,there is no significant differences between realgar and Sanzi Huangshi Formula group.

关 键 词：骨髓增生异常综合征 复方砷剂 三子黄石方 表观遗传学 细胞自噬 

分 类 号：R285.5[医药卫生—中药学]