目的 探讨Patched 1（Ptch1）和胰岛素增强子结合蛋白1（Isl1）在小鼠胚胎前肠的时空表达模式，以及与气管-主支气管早期发育的联系。 方法 取胚龄9.5~12.5d小鼠胚胎各60例，剥取前肠进行Isl1和音猥因子（Shh）蛋白免疫印迹检测；另取胚龄9.5~14.5 d小鼠胚胎各6例制作石蜡连续切片，用抗Isl1、Ptch1、叉头框蛋白A2（Foxa2）、Ⅱ型胶原α1链（Col2a1）、α-平滑肌肌动蛋白（α-SMA）抗体进行免疫组织化学和免疫荧光双标染色，以及HE和Masson染色。 结果 胚龄9.5~12.5 d，小鼠胚胎前肠内胚层Isl1和Shh蛋白表达趋势类似，且Shh表达高峰晚于Isl1。胚龄9.5~12.5 d，前肠向气管发育，Ptch1表达于呼吸内胚层增厚区、外突、喉-气管沟和实心细胞索等相关结构，同时伴有周围Isl1阳性间充质细胞增多和聚集现象，形成以呼吸内胚层及实心细胞索为中心对称的特征性锥体结构；胚龄12.5~13.5 d，主支气管出现，Ptch1仅表达于其外侧壁，同时周围伴有Isl1阳性间充质细胞聚集现象；胚龄13.5~14.5 d，气管-主支气管上皮失去Ptch1表达，周围Isl1阳性间充质细胞也迅速减少。Col2a1阳性软骨细胞最早于胚龄12.5 d出现在紧贴Ptch1阳性气道上皮的Isl1阳性间充质区域；胚龄12.5~13.5 d，Col2a1阳性软骨呈“C”形嵌套在Isl1阳性间充质区域里侧，以近-远端模式发育和扩展；胚龄14.5 d，Col2a1阳性软骨突破Isl1阳性间充质范围向气管背侧扩展，与α-SMA阳性平滑肌呈环形包绕气管。 结论 前肠内胚层Ptch1的表达参与气管-主支气管上皮发育和形态发生，并与气管-主支气管壁Isl1阳性间充质的增殖和聚集关系密切，随后两者共同决定管壁软骨发生的时间、位置和范围。

Objective To explore the spatiotemporal expression patterns of Patched 1 (Ptch1) and insulin enhancer binding protein-1 (Isl1) in mouse embryonic foregut and their relationship with the early development of trachea-main bronchus.    Methods  The foregut of 60 mouse embryos at E9.5-12.5 was separated for the detection of Isl1 and sonic hedgehog (Shh) protein by Western blotting. Serial paraffin sections of 6 mouse embryos at E9.5-14.5 were taken for immunohistochemical staining and immunofluorescence double staining with Isl1, Ptch1, forkhead box protein A2 (Foxa2), type Ⅱ collagen α1 chain (Col2a1) and α-smooth muscle actin (α-SMA), as well as HE staining and Masson staining.   Results  The expression trend of Isl1 and Shh in foregut endoderm at E9.5-12.5 was similar, and the peak of Shh expression was later than Isl1. The foregut developed into the trachea at E9.5-12.5, Ptch1 was expressed in the thickening and protrusion of the respiratory endoderm, the laryngal-tracheal groove and the solid cell cord, accompanied by the increase and aggregation of Isl1-positive mesenchymal cells, forming a characteristic pyramidal structure centered on the respiratory endoderm and the solid cell cord; The main bronchus appeared at E12.5-13.5, Ptch1 was only expressed in its lateral wall, accompanied by the accumulation of Isl1-positive mesenchymal cells; The trachea-main bronchial epithelium lost Ptch1 expression and the surrounding Isl1-positive mesenchymal cells also decreased rapidly at E13.5-14.5.Col2a1-positive chondrocytes first appeared in the Isl1-positive mesenchymal area adjacent to the Ptch1-positive epithelium at E12.5; Col2a1-positive cartilage was nested within the Isl1-positive mesenchymic area in a “C” shape and expanded in a proximal-distal pattern at E12.5-13.5; Col2a1-positive cartilage extended to the dorsal trachea beyond the Isl1-positive mesenchyma and encircles α-SMA positive smooth muscle in a circular manner at E14.5.  Conclusion  The expression of Ptch1 in the foregut endoderm is involved in the development and morphogenesis of the trachea-main bronchus epithelium, and is closely related to the proliferation and aggregation of Isl1-positive mesenchyme in the trachea-main bronchial wall, Subsequently, they jointly determine the time, location and extent of airway cartilage.