关键词: Semaglutide epithelial–mesenchymal transition fibrosis intrauterine adhesions

Mesh : Animals Female Epithelial-Mesenchymal Transition / drug effects Fibrosis Tissue Adhesions / drug therapy metabolism pathology prevention & control Mice Glucagon-Like Peptides / pharmacology Humans Disease Models, Animal Endometrium / drug effects pathology metabolism Transforming Growth Factor beta1 / metabolism genetics Uterus / drug effects pathology metabolism

来  源:   DOI:10.3390/ijms25116196   PDF(Pubmed)

Abstract:
The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.
摘要:
目的探讨塞马鲁肽对宫腔粘连的影响,并发现治疗此类粘连的新药。在这项研究中,用TGF-β1诱导的人子宫内膜上皮细胞模拟细胞模型,通过机械刮治和炎症刺激建立动物模型。与TGF-β1在有或没有不同浓度的塞马鲁肽共培养48小时后,收集细胞进行RT-qPCR和Western印迹分析。每天一次给实验鼠皮下注射三剂,连续两周,对照组接受无菌ddH2O。收集小鼠的血清和子宫组织。HE和Masson染色用于子宫的组织形态学和病理学分析。RT-qPCR和Western印迹用于mRNA和蛋白质表达分析。采用ELISA试剂盒检测血清指标。结果表明,塞马鲁肽显著降低纤维化指标ACTA2、COL1A1、FN和炎症指标TNF-α的mRNA水平,两种模型中的IL-6和NF-κB。塞马鲁肽改善子宫内膜形态,增加子宫内膜腺体的数量,并减少IUA小鼠的胶原沉积。结果还表明,塞马鲁肽可以抑制波形蛋白,E-Cadherin,和两种模型中的N-Cadherin。总之,塞马鲁肽可以改善宫腔粘连的纤维化和炎症,并抑制IUA模型中的上皮-间质转化。
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