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骨髓间充质干细胞可能通过调节miRNA155和miRNA133来改变卵清蛋白诱导的哮喘大鼠的病理变化和免疫反应。

Bone marrow mesenchymal stem cells modified pathological changes and immunological responses in ovalbumin-induced asthmatic rats possibly by the modulation of miRNA155 and miRNA133.

作者信息

Ahmadi Mahdi, Rahbarghazi Reza, Shahbazfar Amir-Ali, Baghban Horeyeh, Keyhanmanesh Rana

机构信息

Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Gen Physiol Biophys. 2018 May;37(3):263-274. doi: 10.4149/gpb_2017052.

Abstract

In the current experiment, we investigated the immune-modulatory potential of mesenchymal stem cells (MSCs) and conditioned media (CM) in attenuating of chronic asthmatic changes in a rat model. Male rats were divided into control (C) and ovalbumin-sensitized (S) groups, which further allocated into three subgroups; rats received systemically 50 μl volume of PBS (C and S groups), CM (CSV and SSV groups) and rats received intravenous infusion of 2 × 106 bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCV and SCV groups). Two weeks later, the expression of interleukin (IL)-4, IL-13, and IL-10, miRNA133, and miRNA155 was measured by real-time PCR. Pathological changes and the recruitment of rBMMSCs into pulmonary parenchyma were evaluated by histopathological and immunofluorescence analyses, respectively. The systemic injection of rBMMSCs, but not CM, decreased the levels of IL-4, IL-13, IL-10, miRNA133, miRNA155 and reduced pathological changes in sensitized rats as compared with other sensitized groups (p < 0.001 to p < 0.05). rBMMSCs transmigrated to lung tissue in cell-administrated rats, albeit intensity of asthmatic changes, in turn, affected the amount of recruited cells. Collectively, our data suggest the potential role of MSCs, but not CM, in reducing pathological changes possibly via the modulation of miRNA133 and miRNA155 during asthmatic changes.

摘要

在当前实验中,我们研究了间充质干细胞(MSCs)和条件培养基(CM)在减轻大鼠模型慢性哮喘变化方面的免疫调节潜力。雄性大鼠被分为对照组(C)和卵清蛋白致敏组(S),每组再进一步分为三个亚组;大鼠全身注射50μl体积的磷酸盐缓冲液(PBS)(C组和S组)、条件培养基(CSV组和SSV组),以及静脉输注2×10⁶骨髓源性间充质干细胞(rBMMSCs)(CCV组和SCV组)。两周后,通过实时聚合酶链反应检测白细胞介素(IL)-4、IL-13、IL-10、miRNA133和miRNA155的表达。分别通过组织病理学和免疫荧光分析评估病理变化以及rBMMSCs向肺实质的募集情况。与其他致敏组相比,全身注射rBMMSCs而非条件培养基可降低致敏大鼠中IL-4、IL-13、IL-10、miRNA133、miRNA155的水平,并减轻病理变化(p<0.001至p<0.05)。在细胞给药的大鼠中,rBMMSCs迁移至肺组织,尽管哮喘变化的强度反过来影响募集细胞的数量。总体而言,我们的数据表明,MSCs而非CM在减轻病理变化方面可能具有潜在作用,这可能是通过在哮喘变化过程中调节miRNA133和miRNA155实现的。

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