mir -141修饰的骨髓间充质干细胞(BMSCs)抑制严重急性胰腺炎的进展

IF 0.1 4区 医学
Wei Su, Yinshan Wu, Huijun Zheng, Xiuliu Guo, Binbin Feng, F. Guo
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引用次数: 0

摘要

骨髓间充质干细胞(BMSCs)对重症急性胰腺炎(SAP)及mirna的治疗作用是目前研究的热点。本研究旨在探讨miR-141修饰的骨髓间质干细胞对SAP的潜在影响。在建立SAP大鼠模型后,将动物分为对照组、模型组、骨髓间质干细胞组、miR-141组、阳性对照组和PI3K/mTOR信号激动剂组(激动剂组),RT-qPCR分析miR-141的表达,Western blot和ELISA分析血清淀粉酶、IL-6、TNF-α、TAP、PI3K、mTOR和LC3-II的表达。miR-141修饰的BMSCs组miR-141显著上调(p > 0.05)。SAP大鼠血清淀粉酶、IL-6、TNF-α、TAP含量升高,骨髓间质干细胞治疗后降低(p < 0.05)。miR-141组的自噬通量降低,阳性对照组的自噬通量升高。模型组和阳性对照组LC3-II、p- pi3k、p- mtor表达最高,BMSCs组和miR-141组次之(p < 0.05)。综上所述,miR-141修饰的骨髓间质干细胞通过降低PI3K和mTOR的磷酸化来抑制PI3K/mTOR信号活性,下调LC3-II蛋白抑制自噬,从而改善SAP的发展,表明miR-141可能是SAP的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
miR-141-Modified Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits the Progression of Severe Acute Pancreatitis
The therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on severe acute pancreatitis (SAP) and miRNAs are currently the research hotspots. This study intends to explore the potential impact of miR-141-modified BMSCs on SAP. After establishment of rat model of SAP, the animals were grouped into control group, model group, BMSCs group, miR-141 group, positive control group, and PI3K/mTOR signaling agonist group (agonist group) followed by analysis of miR-141 expression by RT-qPCR and the expression of serum amylase, IL-6, TNF-α, TAP, PI3K, mTOR, and LC3-II by Western blot and ELISA. miR-141 was significantly up-regulated in the miR-141-modified BMSCs group (p > 0.05). The contents of serum amylase, IL-6, TNF-α, and TAP was increased in SAP rats and decreased after BMSC treatment (p > 0.05). The increased autophagy flux in the rats with SAT was reduced upon treatment with BMSCs and autophagy flux was decreased in miR-141 group but increased in positive control group. The model and positive control group presented highest expression of LC3-II, p-PI3K and p-mTOR, followed by BMSCs group and miR-141 group (p < 0.05). In conclusion, miR-141-modified BMSCs decrease the phosphorylation of PI3K and mTOR to inhibit PI3K/mTOR signaling activity and downregulate LC3-II protein to inhibit autophagy, thereby ameliorating the development of SAP, indicating that miR-141 might be a therapeutic target for SAP.
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