The Roles of Cell Proliferation and Cell Death in Regeneration of Salivary Glands

[引言]本研究旨在阐明大鼠涎腺腺管结扎致萎缩后再生过程中腺泡细胞、导管细胞、肌上皮细胞等实质细胞的增殖与凋亡。[方法]采用金属夹结扎大鼠右颌下腺腺门附近的排泄管，造成大鼠右颌下腺萎缩，结扎后1周（0 d）取出金属夹。从0到14天后取出夹，并与PCNA作为增殖细胞的标记物，TUNEL作为凋亡细胞的标记物，肌动蛋白-PCNA双重免疫组化作为增殖肌上皮细胞的标记物，和透射电子显微镜研究右下颌下腺。[结果]结扎1周后，萎缩腺体内残存导管较多，腺泡较少。在停止结扎后第3天，出现新形成的腺泡，此后数量和成熟度增加。许多残留的和新生的腺泡细胞PCNA阳性反应，尤其是在第4和第5天。PCNA阳性导管细胞随再生时间的延长而减少。双阳性细胞，PCNA阳性肌上皮细胞也观察到，特别是在第2和第4天。在再生过程中发现了一些TUNEL阳性的腺泡和导管细胞。透射电镜下可见部分腺泡和导管细胞有丝分裂和凋亡。此外，在超微结构上首次发现了肌上皮细胞的有丝分裂像。[结论]在萎缩后的下颌下腺再生过程中，残存腺泡细胞和新生腺泡细胞增殖活跃。此外，还存在导管和腺泡细胞的凋亡，其参与实质细胞增殖后的唾液腺组织结构的重塑。此外，还证实了肌上皮细胞能够增殖并参与唾液腺的再生。

【Introduction】The present research aimed to clarify the proliferation and apoptosis of parenchymal cells such as acinar, duct, myoepithelial cells during regeneration of rat salivary glands following atrophy induced by duct ligation.【Methods】Atrophy of the right submandibular gland was induced by excretory duct ligation near its hilum with metal clips, which were removed one week (day 0) after ligation. The right submandibular glands were collected from 0 to day 14 after removal of clips and investigated with PCNA as a marker of proliferating cells, TUNEL as a marker of apoptotic cells, actin-PCNA double immunohistochemistry as a marker of proliferating myoepithelial cells, and transmission electron microscopy.【Results】After one week of ligation, there were many remaining ducts and a few acini in the atrophic glands. At day 3 after discontinuing the ligation, newly formed acini appeared and thereafter increased in number and maturity. many residual and newly formed acinar cells showed positive reaction to PCNA especially at day 4 and 5. The PCNA-positive duct cells decreased in number with the regeneration. Double-positive cells, PCNA-positive myoepithelial cells were also observed, especially between days 2 and 4. A few TUNEL-positive acinar and duct cells were identified during regeneration. Some mitosis and a few apoptosis of acinar and duct cells were also identified by transmission electron microscopy. In addition, a mitotic figure of myoepithelial cell was first identified ultrastructurally.【Conclusions】During regeneration of the submandibular gland after atrophy, both residual and newly formed acinar cells proliferate actively. There is also apoptosis of duct and acinar cells, which participates in remodeling the structure of salivary gland tissue after parenchymal cell proliferation. In addition, it is confirmed that myoepithelial cells are able to proliferate and participate in the regeneration of salivary glands.