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过氧化氢预处理促进脐带静脉间充质干细胞在实验性肺纤维化中的保护作用。

Hydrogen Peroxide Preconditioning Promotes Protective Effects of Umbilical Cord Vein Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis.

作者信息

Mahmoudi Tayebeh, Abdolmohammadi Kamal, Bashiri Hamed, Mohammadi Mehdi, Rezaie Mohammad Jafar, Fathi Fardin, Fakhari Shohreh, Rezaee Mohammad Ali, Jalili Ali, Rahmani Mohammad Reza, Tayebi Lobat

机构信息

Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

出版信息

Adv Pharm Bull. 2020 Jan;10(1):72-80. doi: 10.15171/apb.2020.009. Epub 2019 Dec 11.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H O -preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF). Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 μM for 24 h) of H O . One week following the injection of bleomycin, 2×10 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson's trichrome) and expression of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining. Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (<0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (<0.05) and diminished expression of TGF-β1 and α-SMA. The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF.

摘要

特发性肺纤维化(IPF)是一种进展性肺部疾病,可用的治疗方法很少。间充质干细胞疗法(MSCT)作为一种创新方法,在治疗IPF时具有很高的治疗潜力。根据最近的数据,间充质干细胞的预处理可以提高其治疗效果。我们的研究重点是研究过氧化氢预处理的间充质干细胞(p-MSCs)对博来霉素诱导的肺纤维化(PF)小鼠的抗炎和抗纤维化作用。8周龄雄性C57BL/6小鼠通过气管内(IT)注入博来霉素(4 U/kg)诱导形成PF。分离人脐静脉来源的间充质干细胞(hUCV-MSCs),并将其暴露于亚致死浓度(15 μM,持续24小时)的过氧化氢中。在注射博来霉素一周后,将2×10个间充质干细胞或p-MSCs经气管内注射到实验性PF小鼠体内。记录小鼠的存活率和体重,在注射间充质干细胞14天后,处死所有小鼠。从这些小鼠身上取出肺组织,通过免疫组织化学(IHC)染色检查髓过氧化物酶(MPO)活性、组织病理学变化(苏木精-伊红和Masson三色染色)以及转化生长因子β1(TGF-β1)和α平滑肌肌动蛋白(α-SMA)的表达。与PF+MSC组相比,p-MSCs移植导致结缔组织显著减少(<0.05)和胶原沉积减少。此外,确定PF+pMSC组的肺组织肺泡空间增加(<0.05),TGF-β1和α-SMA的表达减少。结果表明,使用p-MSCs的MSCT可降低博来霉素诱导的PF中的炎症和纤维化因子,同时还能提高MSCT对IPF的治疗效力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaaa/6983995/0e31807a91a0/apb-10-72-g001.jpg

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