南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (11): 1935-1940.doi: 10.12122/j.issn.1673-4254.2023.11.14

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司美格鲁肽对高糖诱导的心肌成纤维细胞增殖的作用研究

李京娟，李凡凡，牛 璐，安斌斌，成晓琼，刘媛媛，王金羊   

  1. 甘肃中医药大学第一临床医学院，甘肃 兰州 730000；甘肃省人民医院内分泌科，甘肃 兰州 730000
  • 出版日期:2023-11-20 发布日期:2023-12-08

Smeglutide inhibits high glucose-induced proliferation of myocardial fibroblasts by downregulating TGFβ/Smad3 signaling

LI Jingjuan, LI Fanfan, NIU Lu, AN Binbin, CHENG Xiaoqiong, LIU Yuanyuan, WANG Jinyang   

  1. First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou 730000, China; Department of Endocrinology, Gansu Provincial People's Hospital, Lanzhou 730000, China
  • Online:2023-11-20 Published:2023-12-08

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摘要： 目的 探讨司美格鲁肽对高糖诱导的心肌成纤维细胞（CFs）增殖中的作用，及其可能的机制。方法 取原代小鼠CFs，通过CFs的特异性抗体波形蛋白Vimentin 鉴定后进行下一步实验。以25 mmol·L-1葡萄糖刺激细胞增殖，5~20 nmol·L-1司美格鲁肽进行干预，并筛选浓度。分别设置正常组：含5.5 mmol·L-1葡萄糖DMEM；高糖组：25 mmol·L-1葡萄糖；司美格鲁肽组：25 mmol·L-1葡萄糖+10 nmol·L-1司美格鲁肽。应用Cell Cycle Staining Kit检测细胞周期；RT-qPCR方法检测α-平滑肌肌动蛋白（α-SMA）、TGF-β1、Smad3 的mRNA表达变化；用ELISA检测Ⅰ型胶原（CoLⅠ）和Ⅲ型胶原（CoLⅢ）。结果 与对照组相比，高糖诱导的CFs增殖明显增强（P<0.05），细胞周期中S期细胞比例增加；与高糖组相比，司美格鲁肽抑制了CFs的增殖（P<0.05），减少CFs细胞周期中S期细胞比例。与对照组相比，高糖组α-SMA、CoLⅠ、CoLⅢ显著增加（P<0.01）；与高糖组相比，司美格鲁肽组α-SMA、CoLⅠ、CoLⅢ显著减少（P<0.01）。与对照组相比，高糖组TGF-β1、Smad3显著增加（P<0.01）；与高糖组相比，司美格鲁肽组TGF-β1、Smad3显著减少（P<0.01）。结论 司美格鲁肽可以抑制高糖诱导的CFs增殖和胶原蛋白的合成，进而发挥抗心肌纤维化的作用，其机制可能与下调TGFβ/Smad3信号通路有关。

关键词: 司美格鲁肽；心肌成纤维细胞；增殖

Abstract: Objective To investigate the effect of semaglutide on high glucose-induced proliferation of cardiac fibroblasts (CFs) and explore its possible mechanism. Methods Primary mouse CFs, identified by detecting vimentin expression, were stimulated with 25 mmol/L and treated with 5-20 nmol/L semaglutide, and the cell proliferation was examined with CKK-8 assay for concentration screening. Cultured CFs exposed to high glucose (25 mmol/L) were treated with 5 nmol/L semaglutide, and the changes in cell cycle were detected using Cell Cycle Staining Kit; The mRNA expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and Smad3 were detected using RT-qPCR, and the levels of type I collagen (CoLⅠ) and type III collagen (CoLIII) in the cell cultures were determined with ELISA. Results Compared with the control cells, the CFs cultured in high glucose exhibited significantly enhanced proliferative activity (P<0.05) with increased percentage of S-phase cells. Semagutide treatment obviously inhibited high glucose-induced proliferation of the CFs (P<0.05) and reduced the percentage of S-phase cells. High glucose stimulation significantly increased the mRNA expressions of α-SMA, CoL Ⅰ and CoLIII in the cells (P<0.01), which were effectively lowered by semaglutide treatment (P<0.01). The expressions of TGF-β1 and Smad3 were significantly increased in high glucose-stimulated CFs (P<0.01) and were lowered by semaglutide treatment (P<0.01). Conclusion Semaglutide can inhibit high glucose-induced proliferation and collagen synthesis in mouse CFs possibly by downregulating the TGFβ/Smad3 signaling pathway.

Key words: semagutide; cardiac fibroblasts; proliferation