Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
复制标题
间充质干细胞衍生的外泌体通过抑制炎症和细胞凋亡改善肾脏缺血再灌注损伤
DOI：
10.3389/fmed.2019.00269
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发表时间：
2019-11-19
影响因子：
3.9
通讯作者：
Zhu, Tongyu
中科院分区：
文献类型：
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作者：
Li, Long;Wang, Rulin;Zhu, Tongyu
本研究旨在探讨间充质干细胞（MSC）保护肾缺血再灌注损伤（IRI）的潜在机制。按照总外泌体分离试剂说明书提取源自MSC的外泌体（MSC-ex）。将大鼠分为五组：假手术组、IRI组、MSC组、MSC-ex组和MSC-ex+RNAase组。 MSCs或MSC-ex通过颈动脉注射。通过肾功能检测和病理学检测来确定MSC-ex对IRI的肾脏保护作用。进行蛋白质印迹和定量逆转录聚合酶链反应（RT-qPCR）来检查凋亡相关蛋白和炎症细胞因子的水平。我们的结果显示，MSC 衍生的外泌体可减轻肾功能障碍、组织学损伤并减少细胞凋亡。 MSC-ex 治疗降低了炎症细胞因子的表达水平，例如白细胞介素 6 (IL-6)、肿瘤坏死因子-α (TNF-α)、核因子 κ B (NF-κB) 和干扰素 γ (IFN-γ)。 IR引起的caspase-9、cleaved caspase-3、Bax和Bcl-2的表达水平也被MSC-ex抑制。 MSC-ex + RNAase组与IRI组具有相似的变化模式，可能是由于RNA水解酶具有消除外泌体功能的能力。我们的结果表明，源自 MSC 的外泌体通过抑制细胞凋亡和炎症反应对 IRI 具有保护作用。我们的研究结果可能为 MSC 治疗肾 IRI 的治疗机制提供新的见解。
This study aimed to investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI). Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five groups: sham-operated, IRI, MSC, MSC-ex, and MSC-ex + RNAase group. MSCs or MSC-ex were injected via carotid artery. The renal function test and pathological detection were applied to determine the renoprotection of MSC-ex on IRI. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to examine the levels of apoptosis-related proteins and inflammatory cytokines. Our results revealed that MSC-derived exosomes attenuated renal dysfunction, histologic damage, and decreased apoptosis. The expression levels of inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), and interferon gamma (IFN-γ), were decreased by the MSC-ex treatment. The expression levels of caspase-9, cleaved caspase-3, Bax, and Bcl-2 caused by IR were also inhibited by MSC-ex. MSC-ex + RNAase group shared the similar pattern of changes with IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes. Our results demonstrated that exosomes originating from MSCs have protective effects on IRI via inhibiting cell apoptosis and inflammatory responses. Out findings may provide a new insight into therapeutic mechanism of MSCs on renal IRI.