摘要
目的在基因水平探讨人类巨细胞病毒(HCMV)感染导致脐血CFU-G损伤的机制,探讨人类脐血造血干细胞(HSC)向粒系祖细胞(CFU-G)增殖过程中hoxa9、hoxa10基因表达的情况。方法从2006年5月至2007年10月收集12例正常足月顺产新生儿断脐后的胎盘段脐血,采用造血干细胞体外培养技术及荧光定量逆转录聚合酶链反应(FQ-RT-PCR)方法,以HCMV-AD169和(或)全反式维甲酸(ATRA)持续干扰HSC,观察正常对照组、ATRA组、HCMV-AD169组、ATRA+HCMV组的造血干祖细胞经人粒细胞集落刺激因子(G-CSF)诱导后,在增殖分化过程中第3、7和12天检测CFU-Ghoxa9、hoxa10基因表达情况。结果各组hoxa9、hoxa10基因均在CFU-G增殖分化的第7天表达量最高(P<0.01),第12天表达量明显减弱(P<0.01),与正常对照组比较,CFU-Ghoxa9、hoxa10基因表达受ATRA(6×10-8mol/L)上调,而受HCMV下调(P<0.01),与HCMV组比较,ATRA可上调HCMV感染的CFU-Ghoxa9、hoxa10基因的表达。结论 CFU-G的增殖分化与hoxa9、hoxa10基因的表达相关。HCMV可能通过调控hoxa9、hoxa10基因表达异常引起造血功能异常,ATRA不仅能显著上调正常CFU-Ghoxa9、hoxa10基因的表达,而且能上调HCMV感染的CFU-Ghoxa9、hoxa10基因的表达。
Objective To observe the expression of hoxa9 gene and hoxa10 gene in the process of the differentiation and proliferation of hematopoietic stem cell to Colony Forming Unit-Granulocyte （CFU-G）in vitro, and to explore the possible mechanism of HCMV-induced maldevelopment to human cord blood Granulocyte Progenitor in genic level. Methods Twelve cases of cord blood were collected from fetal placenta umbilical vein. By the colony culture in vitro, the impact of HCMV-AD169 and ATRA on the CFU-G colony formation was observed, then detect the expression of hoxa9 and hoxa10 genes in the differentiation progress of Hematopoietic Stem Cell （HSC） to CFU-G affected by HCMV and/or ATRA on the third, seventh, and twelfth day. Results Homeobox genes did have a regulatory function in the differentiation process of hematopoiesis. Compared with the expression of hoxa9 and hoxa10 genes on day 3, the quantity of hoxa9 and hoxa10 genes was obviously higher on day 7 and lower on day 12 respectively in each group. Compared with the expression of hoxa9 and hoxa10 genes of normal group, the expression of hoxa9 and hoxa10 of the group ATRA was up-regulated remarkably, while the expression of hoxa9 and hoxa10 of the group HCMV was down-regulated. ATRA was against the down-regulated effect caused by HCMV. Conclusion The hoxa9 and hoxa10 gene are correlated to the manipulation of the proliferation and differentiation of granulocyte progenitor cell. The abnormal expression of hoxa9 and hoxa10 gene induced by HCMV may play an important role in HCMV-induced abnormal hematogenic damage. ATRA （6×10^-8mol/L） can up-regulate the expression of hoxa9 and hoxa10 genes, which confirms the theory that the normal hematopoietic lineage determination and maturation rely on the stable and consistently expression of Homeobox genes.
出处
《中国实用儿科杂志》
CSCD
北大核心
2010年第8期607-610,共4页
Chinese Journal of Practical Pediatrics
基金
四川省教育厅重点科研基金(2004A058)
关键词
巨细胞病毒
粒系祖细胞
全反式维甲酸
hoxa基因
cytomegalovirus
colony forming unit-granulocyte
all-trans retinoic acid
homeobox genes （hoxa）
