E1A激活基因阻遏子表达与小鼠胚胎血管发生的关系  

RELATIONSHIP BETWEEN CREG AND VASCULOGENESIS OF MOUSE EMBRYO

作　　者：韩雅玲[1] 杨桂棠[1] 闫承慧[1] 康建[1] 

机构地区：[1]沈阳军区总医院全军心血管病研究所心内科,沈阳110016

出　　处：《中国组织化学与细胞化学杂志》2007年第5期595-601,共7页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金资助项目(30570664)

摘　　要：目的探讨E1A激活基因阻遏子(CREG)蛋白表达与小鼠动脉形态学发生的关系,了解CREG蛋白在血管发育中的生物学作用。方法制备E9.5d-E18.5d胎鼠、新生1d、28d和2月成鼠不同脏器功能血管的石蜡组织切片,观察主动脉发生过程中的形态学变化;采用免疫组化染色法观察不同发育时相的血管细胞中CREG蛋白和血管平滑肌细胞(vascular smooth muscle cells,VSMCs)标记物肌动蛋白(SMα-actin)的表达变化。结果HE染色显示E9.5d的胚胎血管由单层血管内皮细胞构成,免疫组化显示CREG表达阳性,主要定位于血管壁的单层内皮细胞中,SMα-actin表达为阴性;E10.5d的胚胎血管内皮细胞周围开始出现少量SMα-actin表达阳性的原始VSMCs,同时CREG蛋白表达,定位与SMα-ac-tin蛋白一致。自E12.5d开始SMα-actin蛋白在血管中膜VSMCs中表达增强并持续至成年。CREG蛋白在三层结构的血管细胞中均为阳性表达,其表达强度在E15.5d达到最高,E18.5d表达下降并维持至成年。进一步分析CREG蛋白在成年鼠心、肺、脾和肾等多个脏器血管中的分布,发现所有脏器血管细胞均表达CREG,但表达丰度明显不同,在储存血管和分配血管中CREG蛋白呈高表达,在调节血管中低表达。结论CREG蛋白在小鼠胚胎血管发育早期、持续表达的特点及其在不同脏器功能血管中表达的差异,提示CREG蛋白可能通过调控并维持血管细胞,特别是VSMCs的分化,参与了胚胎血管发生的调控。Objective To investigate the expression of CREG protein in vasculogenesis of mouse embryo and to explore the function of CREG protein in vascular development. Methods Histological haematoxylin-eosin staining and immunohistochemical methods by using anti-SM alpha-actin and anti-CREG were performed respectively in serial 5 μm vessel sections from 9.5-d to 18. 5-d mouse embryos, newborn and mature mice, and functional vessels from different organs of mature mice. Results In 9. 5-d embryos, CREG was expressed only in endothelial cells, while the vascular lumen formed initially. With advanced differentiation, the vascular smooth muscle cells （VSMCs） developed in the embryonic vascular structures; both expressions of SM α-actin protein and CREG were positive and increased gradually in 10. 5-d embryo vessels, while the initial VSMCs occurred. CREG protein had been positive increasing in the adventitial cells as wellas endothelial cells and VSMCs since 12. 5-d till adulthood. It reached the maximum in 15.5-d embryos, and then decreased slightly from El8.5-d to adulthood. CREG expression of different levels was not only seen in large vessel but also in small vessels of different organs such as heart, lungs, spleen and kidneys in adult mice. Conclusion This is the first observation of localization and expression of CREG in embryonic vasculogenesis. The results provide evidence for the suggestion that CREG might play an import.ant role in the regulation of murine vasculogenesis by inducing and maitaining the differentiation of vascular cells, especially VSMCs.

关 键 词：阻遏蛋白 E1A 血管发育 小鼠 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学]