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放射治疗诱导大鼠主要唾液腺实质细胞细胞骨架蛋白的早期改变:一项比较免疫组织化学分析

Early Alterations of Cytoskeletal Proteins Induced by Radiation Therapy in the Parenchymal Cells of Rat Major Salivary Glands: A Comparative Immunohistochemical Analysis.

作者信息

Hassan Sherif S, Alqahtani Mashael S

机构信息

Department of Basic and Clinical Oral Sciences, Umm Al-Qura University, Makkah, SAU.

出版信息

Cureus. 2024 Dec 13;16(12):e75634. doi: 10.7759/cureus.75634. eCollection 2024 Dec.

Abstract

OBJECTIVES

Head and neck malignancies (HNMs) encompass a variety of cancers that affect the oral and para-oral tissues, the most common of which are squamous cell carcinomas. Radiotherapy is commonly used to treat these cancers, often involving radiation exposure to the salivary glands. This study aims to investigate the early impacts of radiotherapy on the internal microstructure of the salivary gland cells and identify which gland exhibits the highest level of radiosensitivity.

METHODS

Twelve male albino rats were divided into two groups (control group and experimental group subjected to radiotherapy). The experimental group underwent a daily dose of 5 Grays of radiotherapy for six days with a total dose of 30 Grays, targeting the salivary glands. One month later, the salivary gland complex was dissected and processed for histological analysis and cytokeratin 17 (CK17) immunostaining.

RESULTS

Histological examination of the irradiated salivary glands revealed atrophic changes in the gland parenchyma, accompanied by the proliferation of dense fibrous stroma. The parenchymal components consisted of small serous acini with poorly defined lumens, many of which had been replaced by fatty tissue with the formation of duct-like structures. Immunohistochemical findings of control glands exhibited weak to mild CK17 expression in duct cells, with the staining pattern typically diffuse or localized to the basal region of the cell. Some serous acini and serous demilunes within mixed acini exhibited diffuse, weak to mild CK17 expression, whereas the mucous acinar cells showed no expression. Radiated major glands revealed moderate to strong CK17 expression in the duct and serous acinar cells (p<0.05). Two distinct expression patterns were identified: the first exhibited diffuse expression across the cells, while the second showed intense expression at the apical region with mild expression at the basal part.

CONCLUSIONS

The positive immunostaining in control salivary glands suggests that small amounts of intermediate filaments are essential for saliva secretion. Radiotherapy significantly disrupts the cytokeratin arrangement and density in major salivary glands, impairing saliva production. The most prominent changes occurred in the submandibular gland, followed by the parotid gland, with the sublingual gland showing the least impact. However, CK17 intensity in acinar cells was highest in the parotid, then submandibular, and lowest in the sublingual gland. Further research is needed to assess the short- and long-term effects and potential for recovery over time.

摘要

目的

头颈部恶性肿瘤(HNMs)包括多种影响口腔及口腔周围组织的癌症,其中最常见的是鳞状细胞癌。放射治疗常用于治疗这些癌症,通常会使唾液腺受到辐射。本研究旨在调查放射治疗对唾液腺细胞内部微观结构的早期影响,并确定哪个腺体表现出最高水平的放射敏感性。

方法

将12只雄性白化大鼠分为两组(对照组和接受放射治疗的实验组)。实验组每天接受5格雷的放射治疗,持续6天,总剂量为30格雷,照射目标为唾液腺。1个月后,解剖唾液腺复合体并进行组织学分析和细胞角蛋白17(CK17)免疫染色。

结果

对接受照射的唾液腺进行组织学检查发现,腺实质出现萎缩性改变,伴有致密纤维间质的增生。实质成分由管腔不清晰的小浆液性腺泡组成,其中许多已被脂肪组织取代,并形成导管样结构。对照组腺体的免疫组织化学结果显示,导管细胞中CK17表达为弱阳性至轻度阳性,染色模式通常为弥漫性或局限于细胞的基底区域。一些混合性腺泡内的浆液性腺泡和浆液半月表现出弥漫性、弱阳性至轻度阳性的CK17表达,而黏液性腺泡细胞则无表达。接受照射的主要腺体在导管和浆液性腺泡细胞中显示出中度至强阳性的CK17表达(p<0.05)。确定了两种不同的表达模式:第一种在细胞中表现为弥漫性表达,而第二种在顶端区域表达强烈,在基部表达轻度。

结论

对照组唾液腺的阳性免疫染色表明,少量中间丝对于唾液分泌至关重要。放射治疗显著破坏了主要唾液腺中细胞角蛋白的排列和密度,损害了唾液生成。最显著的变化发生在下颌下腺,其次是腮腺,舌下腺受影响最小。然而,腺泡细胞中的CK17强度在腮腺中最高,其次是下颌下腺,在舌下腺中最低。需要进一步研究来评估短期和长期影响以及随时间恢复的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a68/11725335/fe66e3632b7a/cureus-0016-00000075634-i01.jpg

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