补肾活血汤调控宫腔粘连大鼠内膜纤维化进程的作用机制研究  

Bushen Huoxue Decoction Regulates Endometrial Fibrosis in Rat Model of Intrauterine Adhesions

作　　者：冯丹[1] 丑丹[1] 张妍 蔡静[2] FENG Dan;CHOU Dan;ZHANG Yan;CAI Jing(Department of Gynecology,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430000,China;Department of Obstetrics and Gynecology,Wuhan Children′s Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430000,China)

机构地区：[1]武汉市中医医院妇科,武汉430000 [2]华中科技大学同济医学院附属武汉儿童医院妇产科,武汉430000

出　　处：《世界中医药》2024年第12期1750-1756,共7页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82274077);湖北省卫健委重点项目(MY2021M019)。

摘　　要：目的:探究微RNA-655(miR-665)/冷诱导核糖核酸结合蛋白(CIRBP)在宫腔粘连(IUA)子宫内膜纤维化中的作用以及补肾活血汤对其的调控作用。方法:使用miRNA靶基因数据库(TargetScan)分析miR-665和CIRBP的结合情况;通过实时定量聚合酶链反应(qRT-PCR)和蛋白免疫印迹技术检测细胞和动物模型中miR-665和CIRBP的转录和表达水平;借助双荧光素酶报告系统和构建过表达载体验证miR-665和CIRBP之间相互调控的作用,以及补肾活血汤对miR-665/CIRBP的调控作用;利用酶联免疫吸附测定(ELISA)和苏木精-伊红(HE)染色检测大鼠宫腔粘连模型中相关因子水平和组织病变程度。结果:在宫腔粘连模型大鼠组织中,CIRBP转录水平显著上升,而miR-665转录水平显著下降。体外实验显示,miR-665模拟物可降低子宫内膜基质细胞中CIRBP的表达水平。此外,补肾活血汤能够降低宫腔粘连的大鼠模型血清中转化生长因子β_(1)(TGF-β_(1))、雌二醇(E_(2))和肿瘤坏死因子-α(TNF-α)的水平。补肾活血汤可以提高miR-665的转录水平并降低CIRBP的表达水平,并减轻大鼠子宫内膜组织的病变程度。结论:补肾活血汤通过调控miR-665/CIRBP途径来减轻宫腔粘连大鼠子宫内膜纤维化程度,为宫腔粘连的治疗提供了新的策略和方向。Objective:To investigate the role of microRNA-665(miR-665)/cold-inducible RNA-binding protein(CIRBP) in endometrial fibrosis in intrauterine adhesion(IUA) and the regulatory effect of Bushen Huoxue Decoction.Methods:TargetScan was used to analyze the binding of CIRBP with miR-665.Quantitative real-time PCR and Western blotting were employed to determine the transcription and expression levels of CIRBP and miR-665 in cells and animal models.The dual-luciferase reporter system and overexpression vector were utilized to examine the mutual regulation between CIRBP and miR-665,as well as the regulatory effects of Bushen Huoxue Decoction on miR-665/CIRBP.Enzyme-linked immunosorbent assay and hematoxylin-eosin staining were performed to measure the levels of relevant factors and pathological changes in the rat model of IUA.Results:The rat model of IUA showed upregulated transcription level of CIRBP and downregulated transcription level of miR-665.The in vitro experiments showed that miR-665 mimics downregulated the expression level of CIRBP in endometrial stromal cells.Bushen Huoxue Decoction lowered the levels of transforming growth factor-β_(1)(TGF-β_(1)),estradiol(E_(2)),and tumor necrosis factor-α(TNF-α) in the serum of the rat model.Additionally,Bushen Huoxue Decoction upregulated the transcription level of miR-665 while downregulating the expression level of CIRBP,thereby alleviating the pathological changes in the endometrial tissue of the rats.Conclusion:Bushen Huoxue Decoction alleviates endometrial fibrosis in the rat model of IUA by regulating the miR-665/CIRBP pathway,which provides new strategies and directions for the treatment of IUA.

关 键 词：宫腔粘连 微RNA-655 冷诱导核糖核酸结合蛋白 补肾活血汤 转化生长因子β_(1) 雌二醇 肿瘤坏死因子-α 

分 类 号：R285.5[医药卫生—中药学]