5-羟色胺对巨核系造血影响.docVIP

5-羟色胺对巨核系造血影响 　【摘要】 5-羟色胺(5-HT)是一种细胞生长因子，主要结合到细胞表面的5-HT1受体、5-HT2受体，通过Ras、MAPK通路促进多种细胞的增殖。在巨核系造血的早期，5-HT通过5-HT2B受体促进造血干细胞及巨核系祖细胞增殖和分化，其具体机制尚未十分清楚；在巨核系造血晚期，5-HT与5-HT2A受体结合促进一氧化氮合成，可能对血小板的释放有一定的影响。另外，5-HT能够对抗血小板α颗粒内容物血小板反应蛋白-1（TPS-1）所引起的巨核细胞凋亡，协同另一内容物血小板源性生长因子（PDGF）引起的巨核细胞增殖，因此5-HT可能是血小板反馈调节中比较重要的物质。本文就5HT及其受体、5HT是细胞生长因子、5HT促进细胞增殖的途径及5HT对巨核系祖细胞的影响进行了综述。 【关键词】 5-羟色胺 　　Effect of 5-Hydroxtryptamine on Megakaryocytopoiesis ——Review 　　Abstract 5-hydroxtryptamine (5-HT，serotonin) has been recognized not only as a neurotransmitter and vasoactive agent，but also as a growth factor.5-HT mainly binds to 5-HT2 receptors or 5-HT1 receptors on cell surface to stimulate cell proliferation through Ras or MAPK pathway in many cell types.It has been reported that 5-HT stimulates megakaryocytopoiesis via 5-HT receptors.The possible mechanism of 5-HT on the proliferation and differentiation of megakaryocytes (MK) has been discussed in this review article.In early stage of megakaryocytopoiesis，5-HT may bind to 5-HT2B receptor on megakaryocytes，and promotes their proliferation and differentiation.In the late stage，5-HT may involve in the platelet release procedure by inducing nitric oxide (NO) synthesis via 5-HT2A receptors.5-HT can also antagonize the apoptotic effect induced by thrombospondin-1 (TSP-1) which is a platelet α granule protein and has synergic effect with platelet-derived growth factor (PDGF) to enhance megakaryocytes proliferation.Therefore，5-HT is likely to be an important substance in the feedback regulation of thrombopoiesis. In this review the 5-HT and its receptors，5-HT as cell growth factor，pathway of 5-HT stimulating cell proliferation and influance of 5-HT on MK-progenitor cells were summarized. 　　Key wards 5-HT; serotonin; megakaryocytopoiesis; platelet 5-羟色胺(5-hydroxtryptamine，5-HT)，早在1941年就由Rapport等从血清中分离出来，是一种具有缩血管活性的物质，并命名为血清紧张素，简称血清素(serotonin)。5-HT既是一种血管活性物质，又是一种神经递质，在中枢及周围神经系统起着重要的生理功能。1986年Nemecek等［1］首先报道5-HT对血管平滑肌细胞的增殖有促进作用；1996年Yang等［2］报道5-HT能促进巨核细胞增殖，因