血小板生成素的研究新进展

Advances in the research of thrombopoietin

血小板生成素(thrombopoietin,TPO)是血小板产生过程中关键性的调节因子,又称巨核细胞生长衍生因子。TPO可与巨核细胞上的表面受体c-Mpl结合,然后再通过多种信号通路来活化巨核细胞,促使巨核细胞发生增殖和分化从而产生血小板,继而达到提高循环中血小板水平的目的。目前,国内外已经对TPO进行了分离和克隆,并对它的蛋白结构、表达调控、生物学活性及其在临床疾病中的治疗效果进行了大量研究。这些研究揭示了TPO的新来源及其与红细胞生成素(erythropoietin,EPO)结构的异同点、TPO在体内浓度的维持机制、各代TPO药物的优缺点;同时也报道了TPO不仅在常见的血小板减少性疾病中具有良好治疗效果,对除外血液系统的其他器官或细胞也有积极的保护作用,如再生障碍性贫血、骨髓增生异常综合征、肝硬化等疾病。这一系列的研究进展发对于TPO的临床应用具有重要的指导意义,本文就上述最新进展作一综述。

Thrombopoietin(TPO) is a key regulator in platelet production, and also known as a megakaryocyte growth-derived factor. TPO can bind to c-Mpl, a surface receptor on megakaryocytes, activate megakaryocytes through a variety of signaling pathways to promote the proliferation and differentiation of megakaryocytes to produce platelets, and then achieve the purpose of increasing platelet levels in circulation. Now, TPO has been isolated and cloned at home and abroad, a lot of research has been done on its protein structure, expression regulation, biological activity and its therapeutic effect in clinical diseases. These studies revealed new sources of TPO and their similarities and differences with erythropoietin(EPO) structure, the maintenance mechanism of TPO concentration in vivo, and the advantages and disadvantages of TPO drugs of different generations. At the same time, TPO was reported not only in common platelets reducing diseases have a good therapeutic effect, and also have positive protective effects on the other organs or cells except the blood system, such as aplastic anemia, myelodysplastic syndrome, liver cirrhosis and so on. This series of research developments has an important guiding significance for the clinical application of TPO. This article reviews the latest developments mentioned above.