补肾方调控淀粉样前体蛋白(APP)防治骨髓抑制综合征的疗效与机制研究

Global cancer situation is extremely severe. Stem cells can be easily damaged during the treatment, causing low hemopoiesis, infection, fracture, high blood sugar and other systemic diseases. It’s essentially a kind of ‘myelosuppression syndrome’. We found that Wnt, BMPs, Notch, AKT, Jak/Stat and other signaling pathways, related with the activity and function of stem cells, got cross talk through amyloid precursor protein (APP) in previous study. On the side of traditional Chinese medicine(TCM), myelosuppression syndrome, with origin in the kidney and pathology in the marrow, is mixed with deficiency and excessiveness, but mainly deficiency. Our previous confirmed that Kidney-Nourishing formula and the active ingredients could regulate the dynamic balance of signaling pathways in stem cells, such as Wnt/ β -Catenin, BMPs, Notch and RNAKL，and then regulate the silence， arousal, proliferation and differentiation of stem cells. Based on this, we put forward the scientific hypothesis: APP may play an important role in myelosuppression syndrome, and Kidney-Nourishing formula and the active ingredients play a therapeutic role by regulation of APP. In this study, following the ‘kidney storing essence, producing marrow " theory as a guide, we will research the effect of APP in myelosuppression syndrome, and explore the curative effect and mechanism of Kidney-Nourishing formula in treating myelosuppression syndrome, through modern biological technology.

全球癌症形势严峻，放化疗极易损伤干细胞，引起造血低下、感染、骨折、高血糖等多系统病症，即“骨髓抑制综合征”，严重危害患者生命健康。前期研究发现Wnt、BMPs、Notch、AKT、Jak/Stat等与干细胞相关的信号通路通过淀粉样前体蛋白（APP）相互串化。中医辨证论治骨髓抑制综合征，认为“ 其本在肾、其病在髓”，“虚实夹杂，以虚为主”。课题组前期证实补肾方及其有效成分能够调控干细胞内Wnt/β-Catenin，BMPs，Notch和RNAKL等信号通路之间的动态平衡，调节其活性和功能。基于此，我们提出科学假设：APP可能在骨髓抑制综合征中发挥重要作用，补肾方及其有效成分可通过调控APP发挥治疗作用。本研究将以“肾藏精，生髓”理论为指导，采用细胞学、组织学、模式动物学等现代生物学研究方法，研究APP在骨髓抑制综合征中的作用，探索补肾方及其有效成分防治骨髓抑制综合征的疗效和作用机制。