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BMSCs 预处理可改善 LPS 诱导的大鼠 DIC 模型中炎症相关的组织破坏。

BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced rat DIC model.

机构信息

Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Wenhua West Road, Jinan, Shandong, China.

出版信息

Cell Death Dis. 2018 Oct 3;9(10):1024. doi: 10.1038/s41419-018-1060-5.

Abstract

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and to further explore the underlying mechanism. A rat model of lipopolysaccharide (LPS)-induced DIC was successfully established, as indicated by impaired plasma hemostatic parameters and damaged organ functions in rats. Importantly, pre-treatment with rat allogeneic BMSCs before LPS injection significantly alleviated systemic intravascular coagulation, reduced plasma levels of organ dysfunction indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi formation, ameliorated liver, heart, and renal injuries, and increased 24-hour survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was in a moderately dose-dependent manner. Further investigation revealed that BMSCs co-cultured with peripheral blood mononuclear cells (PBMCs) significantly inhibited the LPS-stimulated PBMCs proliferation and the release of pro-inflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive factors including indoleamine 2,3-dioxygenase and interleukin-10, which was induced by interferon-γ, contributed to BMSCs-mediated inhibition of LPS-stimulated PBMCs proliferation. These effects do not depend on the direct cell-cell contact. In conclusion, BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be attributed to their anti-inflammatory and immunomodulatory properties, which render BMSCs a promising source for stem cell-based therapeutic approaches in inflammation-related DIC.

摘要

本研究旨在探讨骨髓间充质干细胞(BMSCs)对弥漫性血管内凝血(DIC)模型大鼠的作用,并进一步探讨其潜在机制。成功建立了脂多糖(LPS)诱导的 DIC 大鼠模型,表现为大鼠血浆止血参数受损和器官功能受损。重要的是,LPS 注射前用大鼠同种异体 BMSCs 预处理可显著减轻全身血管内凝血,降低血浆器官功能障碍标志物和促炎细胞因子水平,抑制纤维蛋白微血栓形成,改善肝、心、肾损伤,并提高 LPS 诱导的 DIC 大鼠 24 小时生存率。BMSCs 对 DIC 的保护呈中度剂量依赖性。进一步研究表明,BMSCs 与外周血单个核细胞(PBMCs)共培养可显著抑制 LPS 刺激的 PBMCs 增殖和 PBMCs 释放促炎细胞因子。值得注意的是,干扰素-γ诱导的免疫抑制因子(包括色氨酸 2,3-双加氧酶和白细胞介素-10)的上调有助于 BMSCs 介导的抑制 LPS 刺激的 PBMCs 增殖。这些作用不依赖于直接的细胞-细胞接触。总之,BMSCs 预处理可改善 LPS 诱导的 DIC 模型大鼠的炎症相关组织损伤。BMSCs 的保护作用可能归因于其抗炎和免疫调节特性,使 BMSCs 成为炎症相关 DIC 基于干细胞治疗方法的有前途的来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f976/6170466/253e992ba51f/41419_2018_1060_Fig1_HTML.jpg

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