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超级化激活环核苷酸门控阳离子通道4、连接蛋白43和平足蛋白在小鼠胚胎心的表达与心传导系的发生 被引量:4

Expression patterns of hyperpolarization-activated cyclic nucleotide-gated cation 4,connexin 43 and podoplanin in the embryonic mouse heart and development of cardiac conduction system
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摘要 目的探讨小鼠胚胎心传导系的发生机制。方法用抗心肌肌球蛋白重链(MHC)、抗超级化激活环核苷酸门控阳离子通道4(HCN4)、抗缝隙连接蛋白43(CX43)和抗平足蛋白(podoplanin)抗体,对40只胚龄9~16d小鼠胚胎心进行连续石蜡切片并免疫组织化学或免疫荧光染色。结果胚龄9d,较强的HCN4阳性表达集中在MHC阴性的静脉窦壁,随心脏发育,HCN4较强阳性表达逐渐向窦房结转移。胚龄11d开始,CX43阴性表达显示部位特异性。CX43阴性染色经窦房结沿右心房背侧壁和左、右静脉瓣向房室管背侧壁延伸。胚龄13d,左、右静脉瓣与房间隔底部融合后,进一步延续为房室管背侧壁发育中的CX43阴性染色的房室结,继而与室间隔顶部CX43阴性的房室束相连。胚龄9~10d,在MHC阳性心肌、心包腔背侧壁脏壁中胚层心肌前体细胞及静脉窦周间充质均显示podoplanin阳性表达。胚龄11~13d,podoplanin阳性间充质细胞沿心脏外表面扩展形成podoplanin阳性间皮样心外膜。结论心脏发育早期,主起搏点位于静脉窦壁,起搏电位的产生早于收缩功能的发生。CX43阴性心肌是发育中的心传导系心肌,在胚龄11d即可观察到心传导系早期雏形。podoplanin参与促进心肌前体细胞向心肌细胞的分化。 Objective To investigate the development of the cardiac conduction system of embryonic mouse heart. Methods Serial transverse sections of forty mouse embryonic hearts from embryonic day (ED) 9 to ED 16 were stained immunohistochemically or immunofluorescenfly with antibodies against hyperpolarization-activated cyclic nueleotlde-gated eation 4 (HCN4), myosin heavy chain (MHC), eannexin 43(CX43) and podoplanin. Remalts At ED9, strong positive expression of HCN4 was concentrated in the MHC negative sinus venosus, then gradually shifted to the sineatrial node during the development of the embryonic heart. From ED11 onward, CX43 negative expression showed site-specfie parterre. CX43 negative sineatriai node was seen extending along the dorsal right atrial wall and left and right venous valves towards the dorsal wall of atrioventricular canal. At ED13, with fusion of base of the CX43 negative septum primum, left and right venous valves continued with the developing atrioventricnlar node derived from the dorsal wall of the atrioventricular canal. Developing atrioventricular bundle on the top of the interventricular septum was found connecting with atrioventrieular node. From ED9 to EDIO, strong positive expression of podoplanin was detected both in MHC positive myocardium and in myocardial precursors of splanchnic mesoderm of dorsal perieardial wall and mesenchyme surrounding sinus venosus. Between ED11 and ED13, podoplanin positive mesenehymal cells spread along outer surface of the heart and formed a podoplanin positive mesothelial epicardium. Conclusion At early stage of heart development, the leading pacemaker is located in sinus venous that exhibits function as a pacemaker earlier than contraction. CX43-negative myocardium observed at EDll represents the establishment of the prototype of the developing cardiac conduction system. Podoplanin is involved in promoting myocardial precursor ceils differentiating into cardiocytes.
出处 《解剖学报》 CAS CSCD 北大核心 2012年第3期405-411,共7页 Acta Anatomica Sinica
基金 国家自然科学基金资助项目(30771141) 山西省自然科学基金资助项目(2006011108) 山西省回国留学人员科研资助项目(2008-47) 山西医科大学校青年基金资助项目(02200906) 山西医科大学学生创新项目基金资助项目(2009007)
关键词 胚胎 心传导系 发育 超级化激活环核苷酸门控阳离子通道4 连接蛋白43 平足蛋白 免疫组织 化学 小鼠 Embryo Cardiac conduction system Development Hyperpolarization-activated cyclic nucleotide- gated cation 4 Connexin 43 Podoplanin Immunohistochemistry Mouse
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