常规饲养小鼠与无菌小鼠中应激介导的声带上皮效应比较。

文献信息

中文摘要

引言： 高达25%的嗓音障碍患者报告同时存在心理社会应激，而已被证明心理社会应激可导致喉部微生物组失调。微生物组失调是其他器官疾病病理生理学的基础，通过上皮屏障功能障碍导致失控性炎症。有必要阐明声带（VF）中微生物与非微生物上皮应激通路，以明确心理社会应激如何可能促进VF上皮疾病。
方法： C57BL/6常规饲养（CR）和无菌（GF）成年小鼠被等量分配至应激组和非应激组（n=64，每种小鼠类型/组32只，性别相等）。应激动物完成经过验证的束缚应激方案。应激后收集喉部。在应激、非应激GF和CR小鼠之间比较VF上皮屏障功能障碍的结果。免疫荧光/免疫组织化学测定中膜部VF组织中上皮黏附连接、黏蛋白和增殖的蛋白表达。透射电子显微镜评估VF上皮通透性。
结果： 无论微生物群状态如何，应激动物VF上皮黏附连接、黏蛋白（MUC1、4）的蛋白表达降低，上皮通透性增加。微生物群的存在与应激诱导的上皮增殖增加相关，这一现象在CR小鼠中观察到，但在GF小鼠中未观察到。
结论： 微生物群的存在与应激诱导的VF上皮增殖增加相关。这种增殖增加可能代表对受损细胞的适应性反应，以维持上皮完整性。总体而言，这些发现为确定可用于益生菌疗法的VF上皮靶点提供了基础。
证据等级： 不适用。

英文摘要

INTRODUCTION: Up to 25% of patients with voice disorders report concurrent psychosocial stress, which has been shown to cause laryngeal microbiome dysbiosis. Microbiome dysbiosis underlies disease pathophysiology in other organs, leading to uncontrolled inflammation via epithelial barrier dysfunction. There is a need to delineate microbial versus nonmicrobial epithelial stress pathways in the vocal folds (VF) in order to clarify how psychosocial stress may contribute to VF epithelial disease.
METHODS: C57BL/6 conventionally-raised (CR) and germ-free (GF) adult mice were equally allocated to stressed and unstressed groups (n = 64, 32 per mouse-type/group, equal sexes). Stressed animals completed a validated restraint stress protocol. Following stress, larynges were collected. Outcomes of VF epithelial barrier dysfunction were compared across stressed, unstressed GF, and CR mice. Immunofluorescence/Immunohistochemistry determined protein expression of epithelial adherens junctions, mucins, and proliferation in mid-membranous VF tissue. Transmission electron microscopy assessed VF epithelial permeability.
RESULTS: Regardless of microbiota status, stressed animals had reduced protein expression of VF epithelial adherens junctions, mucins (MUC1, 4) and increased epithelial permeability. Presence of microbiota was associated with stress-induced increases epithelial proliferation, observed in CR, but not GF mice.
CONCLUSION: Presence of microbiota was associated with stress-induced increase in VF epithelial proliferation. This increased proliferation may represent an adaptive response to damaged cells to maintain epithelial integrity. Collectively, these findings provide a foundation for identifying VF epithelial targets that could be leveraged in probiotic-based therapies.
LEVEL OF EVIDENCE: N/A.