摘要
目的:基于miR-181c-3p/信号转导与转录激活因子3(STAT3)通路探讨增液润燥汤对干燥综合征(SS)模型小鼠的作用机制。方法:免疫诱导法制备SS模型小鼠;将BALB/c小鼠随机分为模型组、对照组、白芍总苷组、增液润燥汤低剂量组、增液润燥汤高剂量组、增液润燥汤高剂量+STAT3通路激活剂(Colivelin)组、增液润燥汤高剂量+miR-181c-3p激动剂组,每组3只;测量小鼠日饮水量、唾液流率、颌下腺脏器指数、血沉;ELISA法检测血清免疫球蛋白G(IgG)水平;观察颌下腺组织病理学变化;实时荧光定量PCR检测颌下腺miR-181c-3p的表达;Western blot法检测颌下腺同源异形盒基因A1(HOXA1)、STAT3、磷酸化STAT3(p-STAT3)、白介素-17(IL-17)和叉头盒蛋白P3(Foxp3)的表达;流式细胞仪检测外周血辅助性T细胞17(Th17)/调节性T细胞(Treg)比例。结果:与模型组比较,其余各组小鼠日饮水量、HOXA1、STAT3、p-STAT3、IL-17表达、Th17细胞比例、Th17/Treg明显下降,唾液流率、Foxp3、miR-181c-3p表达、Treg细胞比例明显升高(均P<0.05)。与增液润燥汤高剂量组比较,增液润燥汤高剂量+Colivelin组Treg细胞比例明显下降,日饮水量、Th17细胞比例、Th17/Treg明显升高(均P<0.05)。与增液润燥汤高剂量组比较,增液润燥汤高剂量+miR-181c-3p激动剂组日饮水量、血沉、血清IgG水平、HOXA1、STAT3、p-STAT3、IL-17表达、Th17细胞比例、Th17/Treg明显下降,唾液流率、Foxp3、miR-181c-3p表达、Treg细胞比例显著升高(均P<0.05)。结论:增液润燥汤通过上调SS模型小鼠颌下腺中miR-181c-3p表达,抑制STAT3活化,从而改善Th17/Treg细胞失衡,发挥治疗作用。
Objective:To investigate the mechanism of Zengye Runzao decoction on sjogren’s syndrome(SS)model mice based on miR-181c-3p/signal transducer and activator of transcription 3(STAT3)pathway.Methods:SS model mice were prepared by immune induction.BALB/c mice were randomly divided into model group,control group,total glucosides of paeony capsule group,Zengye Runzao decoction low-dose group,Zengye Runzao decoction high-dose group,Zengye Runzao decoction high-dose+STAT3 pathway activator(Colivelin)group,Zengye Runzao decoction high-dose+miR-181c-3p agonist group,with three mice in each group.The daily water intake,salivary flow rate,submaxillary gland organ index and erythrocyte sedimentation rate were measured.Serum immunoglobulin G(IgG)levels were detected by ELISA.The histopathological changes of submandibular gland were observed.Real-time fluorescence quantitative PCRwas used to detect the expression of miR-181c-3p in submandibular gland.Western blot was used to detect the expression of HOXA1,STAT3,phosphorylated STAT3(p-STAT3),interleukin-17(IL-17)and Foxp3 protein in submandibular gland.Flow analysis was performed to determine the ratio of helper T cell 17(Th17)to regulatory T cell(Treg)in peripheral blood.Results:Compared with model group,the daily water intake,HOXA1,STAT3,p-STAT3,IL-17 expression,Th17 cell proportion and Th17/Treg of mice in other groups were significantly decreased,while the salivary flow rate,Foxp3,miR-181c-3p expression and Treg cell proportion were significantly increased(all P<0.05).Compared with Zengye Runzao decoction high-dose group,the proportion of Treg cells in Zengye Runzao decoction high-dose+Colivelin group was significantly decreased,and the daily water intake,Th17 cell proportion and Th17/Treg were significantly increased(all P<0.05).Compared with Zengye Runzao decoction high-dose group,the daily water intake,ESR,serum IgG level,HOXA1,STAT3,p-STAT3,IL-17 expression,Th17 cell ratio and Th17/Treg in Zengye Runzao decoction high-dose+miR-181c-3p agonist group were significantly d
作者
杨瑞祥
周全
陈慧敏
李纪高
YANG Ruixiang;ZHOU Quan;CHEN Huimin;LI Jigao(The First Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《陕西中医》
CAS
2023年第12期1698-1703,共6页
Shaanxi Journal of Traditional Chinese Medicine
基金
河南省自然科学基金资助项目(202300410254)
河南省中医药科学研究专项课题(2017ZY2022)
河南省第二批中医药青苗人才培养项目[豫卫中医函(2021)16号]。
