人胚胎早期心脏流出道的发育

THE DEVELOPMENT OF THE OUTFLOW TRACT IN THE EARLY EMBRYONIC HUMAN HEART

目的探讨人胚早期心脏流出道的发育机制。方法29例C10～C16期[Carnegie分期法,受精后（22±1～37）d]人胚心脏连续切片,经抗α平滑肌肌动蛋白（α-SMA）、抗α横纹肌肌动蛋白（α-SCA）、抗肌球蛋白重链（MHC）和抗活性Caspase-3抗体免疫组织化学染色,探讨心包腔背侧脏壁中胚层上皮、咽前间充质及动脉囊与心肌性流出道发生的关系。结果人胚发育C10～C15期,由于流出道由颈部向胸部移位及心包腔向胚胎背侧扩展,动脉囊逐渐突向心包腔内,其表面的心包腔背侧脏壁中胚层上皮不断分化为α-SCA和MHC阳性流出道心肌细胞。迁移至流出道动脉端前后壁的咽前间充质在C15期发生凋亡,流出道心肌细胞迁入间充质细胞团内取代凋亡的间充质细胞。C12期始,α-SMA阳性细胞在流出道心内膜垫聚集,参与形成螺旋状流出道嵴。C15～C16期,动脉囊后壁的α-SMA阳性细胞增生,形成主肺动脉隔,将动脉囊分隔为心包内升主动脉和肺动脉干。结论心包腔背侧脏壁中胚层是人胚心脏第二生心区,可不断分化为心肌细胞,使胚胎心肌性流出道长度增加。细胞凋亡染色提示,并非所有迁入流出道的咽前间充质细胞都可分化为心肌细胞。流出道嵴和主肺动脉隔的α-SMA阳性细胞可能来自神经嵴,经不同路线迁移至流出道嵴和主肺动脉隔。

Objective To explore the early development of the outflow tract of the embryonic human heart. Methods Serial sections of twenty-nine human embryonic hearts from Carnegie stage 10 to Carnegie stage 16 were stained immunohjstochemically with antibodies against α-SMA （α-smooth muscle actin）, α-SCA（α-sarcomeric actin）, MHC （myosin heavy chain） and active caspase-3 to investigate the relationship of splanchnic epithelium lining the dorsal wall of the pericardial cavity, the prepharyngeal mesenchyme and the aortic sac with the embryogenesis of the outflow tract myocardium. Results With the caudal translocation of the aortic sac and outflow tract relative to the pharyngeal arches during C10 to C15 and the dorsal expansion of the pericardial cavity on both lateral sides of the outflow tract, the aortic sac originally embedded in the prepharyngeal mesenchyme gradually protruded into the pericardial cavity. The pericardial splanchnic epithelium covering the mesenchymal wall of the aortic sac was found to differentiate progressively into α-SCA and MHC positive cardiomyocytes of the outflow tract. The prepharyngeal mesenchyme migrating to the dorsal and ventral walls of the arterial pole of the outflow tract was seen apoptosed at C15,and the outflow tract cardiomyocytes were detected to proliferate, migrate into and replace the apoptosed outflow tract mesenchymal masses, α-SMA positive cells began to appear in the outflow tract cushions at C12 and gradually aggregated to form two opposite spiral ridges. During C15 and C16, α-SMA positive cells in the posterior wall of the aortic sac proliferated and grew into the aortic sac to form the aorto-pulmonary septum that divided the aortic sac into the intrapeficardial ascending aorta and pulmonary trunk. Conclusion The splanchnic mesodermal epithelium of the pericardial cavity is the secondary heart field of the human embryonic heart, the continuous differentiation of which into cardiomyocytes brings about the increase in the length of the myocardial outflow tract. Cas-3 positive staining suggests that not all of the prepharyngeal mesenchymal cells migrating to the arterial pole of the outflow tract can differentiate into cardiomvocvtes, α-SMA oositive cells in the outflow tract cushions and aorto-pulmonary septum might originate from neural crest, which migrate into outflow tract ridges and the aorto-pulmonary septum at different developmental stages along the different routes.