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人脐带间充质干细胞通过 AKT-mTOR-S6K1 信号通路改善大鼠慢性胰腺炎。

Human umbilical cord-derived mesenchymal stem cells improve chronic pancreatitis in rats via the AKT-mTOR-S6K1 signaling pathway.

机构信息

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Ophthalmology Department, The Yiling Hospital of Yichang, Yichang, Hubei, China.

出版信息

Bioengineered. 2021 Dec;12(1):1986-1996. doi: 10.1080/21655979.2021.1928441.

Abstract

Chronic pancreatitis (CP) is a progressive inflammatory disease. In clinical treatment, many patients cannot get a timely diagnosis and effective treatment due to the lack of early diagnosis indicators. Mesenchymal stem cells have immunomodulatory and anti-inflammatory effects, and have broad application prospects in treating auto-immune diseases and inflammatory diseases. This study aimed to clarify the mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) in the treatment of CP. The rats were randomly divided into four groups, with six rats in each group: control group, CP group, CP + HUCMSCs-treated group I, and CP + HUCMSCs-treated group II. We evaluated the levels of inflammatory factors, fibrosis and apoptosis markers, detected the protein expression levels of AKT-mTOR-S6K1 and assessed histological changes of the pancreas. The results showed that HUCMSCs not only inhibited the secretion of inflammatory cytokines and activation of pancreatic stellate cells but also suppressed the apoptosis of acinar cells. Further investigation revealed that HUCMSCs noticeably suppressed the AKT-mTOR-S6K1 pathway in the pancreatic tissue of DBTC-induced CP. In addition, the therapeutic effect of HUCMSCs injected into the inferior vena cava and left gastric artery in the CP model was also observed, thus providing the basis for the clinical application of intervention measures.

摘要

慢性胰腺炎(CP)是一种进行性炎症性疾病。在临床治疗中,由于缺乏早期诊断指标,许多患者无法得到及时的诊断和有效治疗。间充质干细胞具有免疫调节和抗炎作用,在治疗自身免疫性疾病和炎症性疾病方面具有广阔的应用前景。本研究旨在阐明人脐带间充质干细胞(HUCMSCs)治疗 CP 的机制。将大鼠随机分为四组,每组 6 只:对照组、CP 组、CP+HUCMSCs 治疗组 I 和 CP+HUCMSCs 治疗组 II。我们评估了炎症因子、纤维化和细胞凋亡标志物的水平,检测了 AKT-mTOR-S6K1 蛋白表达水平,并评估了胰腺的组织学变化。结果表明,HUCMSCs 不仅抑制了炎症细胞因子的分泌和胰腺星状细胞的激活,还抑制了腺泡细胞的凋亡。进一步研究表明,HUCMSCs 明显抑制了 DBTC 诱导的 CP 胰腺组织中的 AKT-mTOR-S6K1 通路。此外,还观察了 HUCMSCs 注入下腔静脉和胃左动脉在 CP 模型中的治疗效果,为干预措施的临床应用提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5376/8806739/5f99959c1241/KBIE_A_1928441_UF0001_OC.jpg

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