Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Preventive Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Int J Mol Med. 2020 Jul;46(1):179-190. doi: 10.3892/ijmm.2020.4598. Epub 2020 May 12.
Amoxicillin is a common pediatric drug. However, to the best of our knowledge, the role of amoxicillin in enamel hypomineralization has not yet been fully elucidated. The aim of the present study was to assess the effects of amoxicillin on enamel mineralization, the morphology of ameloblasts, as well as the expression of kallikrein‑related peptidase 4 (KLK4), and the tight junction proteins, claudin 1 (CLDN1), claudin 4 (CLDN4) and occludin (OCLN), in ameloblasts of juvenile mice. A total of 36 3‑day‑old Kunming mice were randomly divided into three groups. The mice were administered 0, 50 or 100 mg/kg amoxicillin by intragastric administration for 19 days. The surface morphology and calcium (Ca), phosphorous (P) and carbon contents of mandibular incisors and first molars were examined by scanning electron microscopy and energy dispersive X‑ray spectroscopy. Histological changes in the ameloblasts of mandibular incisors were analyzed by hematoxylin and eosin staining. The KLK4, CLDN1, CLDN4 and OCLN expression levels of ameloblasts were observed by immunohistochemical staining. The incidence of white patches in the incisor was 100% in the 100 mg/kg amoxicillin‑treated groups. A greater number of enamel defects were observed in the incisal/occlusal half of mandibular incisors/molars compared with in the cervical half in the amoxicillin‑treated groups. Following phosphoric‑acid treatment, the enamel rod and interrod were aligned in a disorderly manner in the amoxicillin‑treated groups. Amoxicillin decreased the Ca/P ratio in the enamel of mandibular incisors and molars. More intercellular spaces among maturation ameloblasts were observed in the amoxicillin‑treated groups. Amoxicillin decreased KLK4 and CLDN1, CLDN4 and OCLN expression in mature ameloblasts. The administration of amoxicillin in juvenile mice induced enamel hypomineralization, and the effects of amoxicillin on enamel hypomineralization may be mediated via multiple pathways.
阿莫西林是一种常见的儿科药物。然而，据我们所知，阿莫西林在釉质矿化不全中的作用尚未完全阐明。本研究旨在评估阿莫西林对幼年小鼠成釉细胞矿化、成釉细胞形态以及激肽释放酶相关肽酶 4（KLK4）和紧密连接蛋白 Claudin-1（CLDN1）、Claudin-4（CLDN4）和 Occludin（OCLN）在成釉细胞中的表达的影响。将 36 只 3 日龄昆明小鼠随机分为三组，分别给予 0、50 或 100mg/kg 阿莫西林灌胃 19 天。通过扫描电子显微镜和能谱分析检测下颌切牙和第一磨牙的表面形态和钙（Ca）、磷（P）和碳含量。通过苏木精-伊红染色分析下颌切牙成釉细胞的组织学变化。通过免疫组织化学染色观察成釉细胞中 KLK4、CLDN1、CLDN4 和 OCLN 的表达水平。在 100mg/kg 阿莫西林处理组中，切牙的白色斑块发生率为 100%。与颈半相比，在阿莫西林处理组中，下颌切牙/磨牙切缘/牙合面的釉质缺陷数量更多。经磷酸酸蚀处理后，在阿莫西林处理组中，釉柱和釉间柱排列紊乱。阿莫西林降低了下颌切牙和磨牙釉质的 Ca/P 比值。在阿莫西林处理组中，成熟成釉细胞之间的细胞间隙更多。阿莫西林降低了成熟成釉细胞中 KLK4 和 CLDN1、CLDN4 和 OCLN 的表达。在幼年小鼠中给予阿莫西林会导致釉质矿化不全，而阿莫西林对釉质矿化不全的影响可能通过多种途径介导。
