青黄散经线粒体介导MDS核基因组甲基化和HIF-1α表达调控的机制研究

青黄散治疗骨髓增生异常综合征（MDS）临床疗效确切，能够明显改善外周血象。我们前期的研究已证明MDS患者经过青黄散治疗后TRAF3等多种核抑癌基因发生去甲基化， HIF-1α表达水平提高，线粒体DNA的异常拷贝数能够明显减少伴见氧化应激。基于前期研究结果我们提出以下假说：青黄散可能通过调控MDS患者骨髓单个核细胞的线粒体的中间代谢产物α-KG，调节TET酶和PHD酶的活性，进而对核抑癌基因的高甲基化水平和HIF-1α水平产生调控，在阻遏MDS向AML转化的同时促进红系造血。研究拟从SKM-1细胞株培养和临床MDS患者两个层面证实青黄散通过调控MDS线粒体的中间代谢产物α-KG对核抑癌基因的高甲基化水平和HIF-1α水平产生影响，并通过分析青黄散治疗MDS发挥临床疗效的生物能量代谢调控机制，探索靶向肿瘤细胞生物能量代谢的新靶点。

Qinghuang Powder has definite clinical effect on MDS and can improve the peripheral blood counts. Our previous studies have shown that after treatment with Qinghuang powder, many nuclear tumor suppressor genes, such as TRAF3, have been demethylated, HIF-1α expression level has been increased, and abnormal copy numbers of mitochondrial DNA can significantly reduce oxidative stress. Based on the results of previous studies, we proposed the following hypothesis: Qinghuang Powder may regulate the activity of TET and PHD enzymes by regulating the intermediate metabolite α- KG of mitochondria of MDS patients' bone marrow mononuclear cells, and then regulate the production of HIF-1α and hypermethylation level of nuclear tumor suppressor genes, so as to inhibit the transformation of MDS to AML and promote erythropoiesis at the same time. In this research, it is proposed to confirm that Qinghuang Powder has an effect on the the production of HIF-1α and hypermethylation level of nuclear tumor suppressor genes by regulating the intermediate metabolite α-KG of mitochondria from two aspects of SKM-1 cell line culture and clinical MDS patients, and to explore a new target of biological energy metabolism of tumor cells by analyzing the biological energy metabolism regulation mechanism of Qinghuang Powder in the treatment of MDS.