State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Science, 2019RU066, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2024 Jun 4;25(11):6196. doi: 10.3390/ijms25116196.
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.
本研究旨在探讨司美格鲁肽对宫腔粘连的作用，为宫腔粘连寻找新的治疗药物。本研究通过 TGF-β1 诱导的人子宫内膜上皮细胞建立细胞模型，通过机械刮宫和炎症刺激建立动物模型。将细胞与 TGF-β1 共培养 48 小时，分别加入不同浓度的司美格鲁肽，收集细胞进行 RT-qPCR 和 Western blot 分析。实验小鼠每天皮下注射 3 个剂量的司美格鲁肽，连续 2 周，对照组注射无菌 ddH2O。收集小鼠血清和子宫组织，HE 和 Masson 染色观察子宫组织形态学和病理学变化，RT-qPCR 和 Western blot 检测纤维化和炎症相关基因及蛋白的表达，ELISA 试剂盒检测血清学指标。结果表明，司美格鲁肽可显著降低两种模型中纤维化指标 ACTA2、COL1A1 和 FN 及炎症指标 TNF-α、IL-6 和 NF-κB 的 mRNA 水平。司美格鲁肽改善了宫腔粘连小鼠的子宫内膜形态，增加了子宫内膜腺体数量，减少了胶原沉积。结果还表明，司美格鲁肽可抑制两种模型中 vimentin、E-Cadherin 和 N-Cadherin 的表达。综上，司美格鲁肽可改善宫腔粘连的纤维化和炎症反应，抑制上皮间质转化。
Zotero 插件
