围绝经期干眼症患者miR-98、TLR4表达及与泪液分泌功能的关系

Expression of miR-98 and TLR4 in perimenopausal patients with dry eye syndrome and their relationship with tear secretion function

目的 探究围绝经期干眼症患者微小RNA(miR)-98、Toll样受体4(TLR4)表达及与泪液分泌功能的关系。方法 选取2021年12月至2023年12月该院收治的围绝经期干眼症患者126例(252眼)为干眼组,选取同期围绝经期的体检健康女性126例(252眼)作为对照组。测定结膜上皮细胞、泪液中miR-98、TLR4水平;采用Pearson法分析miR-98、TLR4水平之间的相关性及其与炎症因子[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α]、泪液分泌功能[泪膜破裂时间(BUT)、基础泪液分泌试验(SⅠt)]的相关性;采用Spearman相关分析miR-98、TLR4水平与角膜荧光素染色(CFS)评分的相关性。结果 与对照组相比,干眼组结膜上皮细胞、泪液中的miR-98相对表达水平明显降低(P<0.05),TLR4、TNF-α、IL-1β、IL-6水平明显升高(P<0.05)。围绝经期干眼症患者结膜上皮细胞、泪液中miR-98与TLR4呈负相关(r=-0.418、-0.519,P<0.05)。与对照组相比,干眼症组CFS评分升高(P<0.05),BUT、SⅠt缩短(P<0.05)。miR-98在结膜上皮细胞、泪液中与TNF-α、IL-1β、IL-6、CFS评分呈负相关(P<0.05),与BUT、SⅠt呈正相关(P<0.05)。TLR4在结膜上皮细胞、泪液中与TNF-α、IL-1β、IL-6、CFS评分呈正相关(P<0.05),与BUT、SⅠt呈负相关(P<0.05)。多因素Logistic回归分析显示,结膜上皮细胞、泪液中miR-98及SⅠt是影响围绝经期发生干眼症的保护因素(P<0.05),结膜上皮细胞、泪液中TLR4、TNF-α、IL-1β、IL-6及CFS评分是影响围绝经期发生干眼症的危险因素(P<0.05)。结论 围绝经期干眼症患者结膜上皮细胞、泪液中miR-98相对表达水平降低,TLR4水平升高,与炎症反应、泪液分泌功能密切相关。

Objective To explore the expression of microRNA(miR)-98 and Toll-like receptor 4(TLR4) in perimenopausal patients with dry eye syndrome and their relationship with tear secretion function.Methods A total of 126 perimenopausal patients with dry eye syndrome(252 eyes) admitted to the hospital from December 2021 to December 2023 were selected as the dry eye group,and 126 menopausal healthy female who underwent physical examination(252 eyes) during the same period were selected as the control group.The levels of miR-98 and TLR4 in conjunctival epithelial cells and tears were measured.Pearson method was applied to analyze the correlation between miR-98 and TLR4 levels,and their correlation with inflammatory factors [interleukin(IL)-1,IL-6,tumor necrosis factor(TNF)-α] and tear secretion function [break-up time(BUT),Schirmer Ⅰ test(SⅠt)].Spearman correlation was applied to analyze the correlation between miR-98,TLR4 levels and corneal fluorescein staining(CFS) score.Results Compared with the control group,the relative expression level of miR-98 in conjunctival epithelial cells and tears in the dry eye group was obviously reduced(P<0.05),while the levels of TLR4,TNF-α,IL-1,and IL-6 were obviously increased(P<0.05).miR-98 and TLR4 in conjunctival epithelial cells and tears of perimenopausal patients with dry eye syndrome were negatively correlated(r=-0.418,-0.519,P<0.05).Compared with the control group,CFS score in the dry eye group was increased(P<0.05) and BUT and SⅠt were shortened(P<0.05).miR-98 was negatively correlated with TNF,IL-1,IL-6 and CFS score in conjunctival epithelial cells and tears(P<0.05),and positively correlated with BUT and SⅠt(P<0.05).TLR4 was positively correlated with TNF-α,IL-1β,IL-6 and CFS score in conjunctival epithelial cells and tears(P<0.05),and negatively correlated with BUT and SⅠt(P<0.05).Multivariate Logistic regression analysis showed that miR-98 in conjunctival epithelial cells and tears and SⅠt were protective factors affecting the occurrence of dry eye syndrome during perimenopause(P<0.05),while TLR4,TNF-α,IL-1β,IL-6 in conjunctival epithelial cells and tears and CFS score were risk factors affecting the occurrence of dry eye syndrome during perimenopause(P<0.05).Conclusion In perimenopausal patients with dry eye syndrome,the relative expression levels of miR-98 in conjunctival epithelial cells and tears decrease,while TLR4 levels increase,which are closely related to inflammation and tear secretion function.