成骨生长肽羧基端片段及其衍生物对骨髓抑制小鼠造血系统的影响

摘要

目的:初步观察成骨生长肽羧基端片段[OGP(10-14)]及其衍生物G38I、G38K对环磷酰胺(CTX)诱导骨髓抑制小鼠造血系统的影响.方法:40只小鼠随机分为5组,经注射CTX诱导骨髓抑制.分别给予OGP(10-14)、G38I、G38K或粒细胞集落刺激因子(G-CSF)治疗,未治疗的CTX组为阴性对照.分别于第1、7、10、14天测定小鼠外周血象并于注射CTX后第7天处死.观察外周血干细胞抗原-1(Sca-1)阳性细胞比例和骨髓有核细胞数.结果:注射CTX可诱导小鼠出现骨髓抑制.注射CTX前OGP(10-14)及其衍生物对小鼠外周血象无明显作用(P>0.05).注射CTX后OGP(10-14)组和G38I组外周血白细胞较CTX组显著升高(P<0.01),疗效与G-CSF接近,G38I组和G38K组血小板升高(P<0.01).各药物治疗组外周血Sca-1阳性细胞百分比和骨髓有核细胞数显著提高(P<0.05,P<0.01).结论:OGP(10-14)及其衍生物G38I、G38K可升高骨髓抑制小鼠外周血白细胞和血小板的数量,动员造血干细胞,对骨髓造血功能的恢复起到积极作用.%Objective To investigate the effects of osteogenic growth peptide c-terminal pentapeptide [OGP(10-14)] and its derivatives G38I, G38K on hematopoiesis in mice with cyclophosphamide (CTX)-induced bone marrow depression. Methods Forty mice were randomly divided into 5 groups. The bone marrow depression models were induced by injection of CTX. The mice were treated by OGP (10-14), G38I and G38K or granulocytecolony-stimulating factor (G-CSF) respectively, while the untreated CTX group was negative control.The peripheral blood cells counts were performed four times (at the 1st, 7th, l0th, 14th day). All the mice were sacrificed on the 7th day after CTX injection. The percentage of stem cell antigen-1 (Sca-1) positive cells in peripheral and bone marrow nucleated cells (BMNC) were examined. Results CTX induced bone marrow depression in mice. OGP(10-14) and its derivatives hadn't effects before CTX injection(P ＞ 0.05)but the white blood cells (WBC) of OGP(10-14) and G38I were increased obviously after CTX injection (P ＜ 0.01 ). Blood platelets (PLT) were increased in G38I and G38K groups (P ＜ 0.01 ). The percentage of Sca-1 positive cells in peripheral blood and BMNC increased in all treated groups (P ＜ 0.05, P ＜ 0.01 ). Conclusions OGP(10-14) and its derivatives G38I and G38K may enhance the WBC and PLT in mice with bone marrow depression, mobilize the hematopoietic stem cells and perform an positive effect on the recovery of hematopoiesis.