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目的探讨骨形态发生蛋白-2(BMP-2)在小鼠胚胎心流出道发育过程中的作用。方法对胚龄9d(E9)~E15(各胚龄取3~7只)小鼠心连续石蜡切片,用抗α-横纹肌肌动蛋白(α-SCA)抗体、抗胰岛素增强子结合蛋白(ISL-1)抗体、抗增殖细胞核抗原(PCNA)抗体、抗BMP-2抗体进行免疫组织化学染色。结果 E9,流出道心胶质内无细胞,心肌增殖活性低,BMP-2弱表达于流出道心肌、心内膜及心包腔背侧壁。E9~11,流出道增长,心包腔背侧壁ISL-1阳性细胞至流出道远端分化为心肌细胞后增殖逐渐减弱。E10~11,流出道嵴内间充质细胞逐渐增加,可见BMP-2、PCNA阳性细胞;流出道BMP-2表达逐渐增强达高峰,向两端延伸逐渐减弱,动脉端可及心包反折处。E12,流出道缩短,BMP-2表达减弱。E13~15,流出道隔逐渐肌化,BMP-2在心脏近大血管部心肌呈较弱表达。E10~13,流出道远段心肌呈低增殖活性,近段及右心室心肌增殖成小梁致右心室形成及扩大。结论 BMP-2诱导第二生心区(SHF)细胞分化为心肌细胞添加至心动脉端,参与心流出道嵴的发育。BMP-2抑制流出道心肌增殖,流出道近段BMP-2表达减弱重启了心肌细胞增殖,致右心室形成及流出道缩短。低水平的BMP-2可能诱导流出道隔间充质细胞向心肌分化。
Objective To investigate the role of bone morphogenetic protein-2 (BMP-2) in the development of mouse embryo cardiac outflow. Methods Heart continuous paraffin sections from 9 days (E9) to E15 (3 to 7 embryos of each age) were treated with anti-α-SCA antibody, anti-insulin enhancer binding protein -1) antibody, anti-proliferating cell nuclear antigen (PCNA) antibody, and anti-BMP-2 antibody for immunohistochemical staining. Results E9, outflow tract glial cells without cells, low proliferation activity of myocardial, BMP-2 expression in the outflow tract myocardium, endocardial and pericardial dorsal wall. E9 ~ 11, outflow tract growth, pericardial dorsal wall ISL-1 positive cells to the outflow tract distal differentiation into cardiomyocytes gradually decreased proliferation. E10-11, out of the ridge crest of mesenchymal cells gradually increased, showing BMP-2, PCNA positive cells; outflow tract gradually increased expression of BMP-2 up to the peak, to both ends of the stretch gradually weakened, the arterial end and pericardial fold . E12, outflow tract shortening, BMP-2 expression weakened. E13 ~ 15, outflow tract septum gradually muscle, BMP-2 in the heart near the major vascular weak myocardial expression. E10 ~ 13, outflow tract distal myocardial was low proliferative activity, proximal and right ventricular myocardial proliferation into trabecular to the right ventricle formation and expansion. Conclusion BMP-2 induces cardiomyocytes to differentiate into cardiomyocytes in the second heart region (SHF) and participates in the development of the cardiac outflow cristae. Inhibition of BMP-2 outflow tract myocardial proliferation, outflow tract proximal BMP-2 expression weakened restart of myocardial cell proliferation, causing the formation of the right ventricle and outflow tract shortening. Low levels of BMP-2 may induce outflow tract mesenchymal cells to differentiate into cardiac muscle.