Atorvastatin Improves Survival of Implanted Stem Cells in a Rat Model of Renal Ischemia-Reperfusion Injury
Atorvastatin Improves Survival of Implanted Stem Cells in a Rat Model of Renal Ischemia-Reperfusion Injury
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DOI：
10.1159/000362623
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Ding, Xiaoqiang
中科院分区：
文献类型：
--
作者：
Cal, Jieru;Yu, Xiaofang;Ding, Xiaoqiang
目的：探讨阿托伐他汀联合骨髓间充质干细胞移植治疗大鼠急性肾损伤的疗效。研究方法：结扎大鼠双侧肾蒂45 min后，松开肾蒂夹，造成肾缺血再灌注（I/R）模型。再灌注后，立即通过用或不用Ator预处理的动物的颈动脉给予CM-Dil标记的MSC（1 × 10（6）个细胞）或仅载体。结果如下：Ator + MSCs联合治疗可显著降低I/R损伤后24 h血清肌酐和血尿素氮的升高水平，减轻肾损害程度。此外，与其他组相比，Ator+MSCs组肾小管细胞凋亡抑制，增殖促进。与肾功能和形态的改善一致，Ator预处理显著改善了氧化应激，抑制了炎症反应，并增加了植入的MSC的活力。关于进一步的机制，我们发现，Toll样受体4（TLR 4）和高迁移率族蛋白1的表达，先天免疫的潜在介质，在Ator治疗组显着降低。结论：Ator治疗可以通过抑制TLR 4信号传导来保护I/R损伤的肾脏，为移植的MSC的存活创造更好的环境。Ator+ MSC联合治疗的额外益处可能是由于Ator介导的对缺血肾脏中氧化应激和炎症的抑制。(C)2014 S. Karger AG，巴塞尔
Aims: To investigate the impacts of combinatorial atorvastatin (Ator) perioperative administration and mesenchymal stem cell (MSC) implantation on therapeutic effects in the rat experimental acute kidney injury. Methods: The model of renal ischemia-reperfusion (I/R) injury was induced by the release of bilateral renal pedicle clamps following 45 min of occlusion. Immediately after reperfusion, CM-Dil-labeled MSCs (1 x 10(6) cells) or vehicles only were administered through the carotid artery of the animals pretreated with or without Ator. Results: The combined treatment with Ator and MSCs (Ator+MSCs) markedly reduced the elevated levels of serum creatinine and blood urea nitrogen, as well as the severity of renal damage 24 h after I/R injury. In addition, we also observed inhibition of renal tubular cell apoptosis and promotion of proliferation in the Ator+MSCs group compared with the other groups. Consistent with the improvement in renal function and morphology, Ator pretreatment significantly ameliorated oxidative stress, inhibited inflammation response, and increased the viability of implanted MSCs. With regard to the further mechanism, we found that the expression of Toll-like receptor 4 (TLR4) and high-mobility group box 1, potential mediators of innate immunity, was significantly decreased in the Ator-treated groups. Conclusion: Ator treatment may protect the kidney undergoing I/R injury through suppression of TLR4 signaling, creating a better environment for the survival of grafted MSCs. The extra benefit of the Ator+MSCs combined therapy may result from the Ator-mediated inhibition of oxidative stress and inflammation in the ischemic kidney. (C) 2014 S. Karger AG, Basel