褪黑素对照射后小鼠血小板造血的保护作用

Protective effect of melatonin on thrombocytopoiesis in irratiated mice

目的探讨褪黑素(melatonin,Mel)对照射后小鼠血小板和巨核细胞造血功能的影响。方法18只雌性BALB/c小白鼠随机分为3组正常组(N组),对照组(C组)和Mel组(M组),每组6只。其中N组不接受照射和药物注射,C组和M组小鼠予4Gy的60Coγ射线全身照射,照射后M组每天腹腔注射Mel10mg.kg-1.d-1,连续注射21d,C组注射生理盐水。于照射前及照射后的第7、14和21天采尾血,观察白细胞和血小板计数变化,在第21天采血后取骨髓行巨核细胞集落形成单位(CFU-MK)和骨髓基质细胞集落形成单位(CFU-F)培养。另外观察正常小鼠体外骨髓CFU-MK在不同浓度的Mel(0～500nmol/L)作用下的生长情况。结果M组血小板计数回升明显高于C组(P<0.05),M组的CFU-MK和CFU-F集落生长明显优于C组(P<0.001)。体外小鼠骨髓CFU-MK的生长对Mel有浓度依赖性,Mel浓度为200nmol/L时,CFU-MK集落数目最多,且集落大小和MK成熟度较对照均有明显提高。结论Mel对照射后小鼠骨髓的血小板造血功能有保护作用,Mel可促进骨髓基质细胞和MK增殖分化,从而提升外周血血小板数量。

Objective To study the protective effect of melatonin on thrombocytopoiesis（T） and its mechanism in total-bedily irradiated mice. Methods Altogether 18 female BALB/c mice were randomly divided into three experimental groups （6 each） ： Group 1 （normal control, N） received neither irradiation nor melatonin; Group 2 （model control, C）; received total body-irradiation for 4 Gy gama-rays and Group 3（melatonin, M）, received melatonin after irradiation at the dosage of 10 mg· kg^- 1· d^- 1 via i. p. injection in consecutive 21 days. In Group C normal saline instead of melatonin was administered in the same way as above. Peripheral blood platelets and white blood cells（WBC） were analyzed for the three groups on day 0,day 7,day 14, and day 21. AU the mice were sacrificed to collect bone marrow cells for the assays of colony-forming unit-megakaryocyte （CFU-MK） and of colony-forming unit-fibroblast （CFU-F）. The effects of melatonin of different concentrations （0-500 nmol/ L） on CFU-MK formation were observed in vitro. Results The results showed that melatonin enhanced the recovery of T. Moreover, melatonin also promoted the increase of CFU-F （28 ±10.4 vs 14.6 ± 2.8） and CFU- MK （19.63 ± 3.28 vs 11 ± 2.24） in vivo. The amount of CFU-MK in vitro was dependent on the concentration of melatonin. Compared with the control group, the size of CFU-MK in Group M was much larger and MK cells were more mature, especially when the melatonin concentration was 200 nmol/L. Conclusion Melatonin provides protective effect on T in irradiated mice. It enhances T in vivo and promotes the growth of bone marrow stromal cells as well as megakaryocytes in vitro. Therefore, we speculate that the T-protective activity of melatonin may be mediated via promoting growth of the progenitors of platelet, megakaryocytes, and bone marrow stromal cells.