Cisplatin has been hypothesized to induce nephrotoxicity through triggering the apoptosis of tubular cells; however, the drug remains widely administered for the treatment of tumors. Recently, mesenchymal stem cells (MSCs) have been demonstrated to protect the kidney from the adverse effects induced by cisplatin. The aim of the present study was to investigate the mechanisms underlying the protective effects of human adipose-derived MSCs (AD-MSCs) on kidney function and tubular cells. Sprague-Dawley rats were divided into three groups, which included the healthy controls, those subjected to cisplatin-induced acute kidney injury (AKI) for 24 h without subsequent treatment and those subjected to cisplatin-induced AKI for 24 h, followed by AD-MSC engraftment. The rats were sacrificed at day 5 and the effects were analyzed using various methods, including biochemical analysis, structural examination and cell tracking experiments. In addition, an in vitro experiment with NRK-52E cells was performed. The cells were divided into three groups, including the healthy control, cisplatin induction and cisplatin induction with co-culture of AD-MSCs, and were subsequently assessed with a Transwell assay. After culture for four days, the cells were lysed and the total protein extract was subjected to western blot analysis. Cisplatin-induced renal dysfunction and tissue damage was shown to recover following AD-MSC infusion, although there were few AD-MSCs observed around the injured kidney tubules in the kidney. When the cisplatin-treated NRK-52E cells were co-cultured with AD-MSCs, the activation of p38 and BAX were inhibited, while the expression of Bcl-2 was upregulated, as compared with the cisplatin-treated NRK-52E cells that were not co-cultured. Therefore, AD-MSCs were shown to markedly improve cisplatin-induced renal failure and tubular cells necrosis through the secretion of certain factors, which subsequently inhibited the apoptosis pathway in vitro. It was hypothesized that AD-MSC secretion was triggered by the injured tubular cells. Thus, AD-MSCs may be important for the therapy of patients with renal injury due to their antiapoptotic capacity.

中文翻译：

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人脂肪来源的间充质干细胞通过抗凋亡途径修复顺铂诱导的急性肾损伤。

据推测，顺铂通过触发肾小管细胞的凋亡诱导肾毒性。然而，该药物仍被广泛用于治疗肿瘤。最近，间充质干细胞（MSCs）已被证明可以保护肾脏免受顺铂引起的不良影响。本研究的目的是研究人类脂肪来源的MSC（AD-MSC）对肾脏功能和肾小管细胞的保护作用的潜在机制。将Sprague-Dawley大鼠分为三组，包括健康对照组，未经顺铂治疗顺铂诱导的急性肾损伤（AKI）24小时，顺铂诱导AKI进行24 h，然后进行AD-治疗的三组。 MSC植入。在第5天处死大鼠，并使用多种方法分析其作用，包括生化分析，结构检查和细胞跟踪实验。此外，还进行了NRK-52E细胞的体外实验。将细胞分为三组，包括健康对照，顺铂诱导和与AD-MSC共培养的顺铂诱导，随后用Transwell测定法评估。培养四天后，裂解细胞，并对总蛋白提取物进行蛋白质印迹分析。尽管在肾脏中受损的肾小管周围观察到的AD-MSC很少，但顺铂诱导的肾功能不全和组织损伤已在AD-MSC输注后恢复。当顺铂处理过的NRK-52E细胞与AD-MSC共培养时，p38和BAX的激活受到抑制，而Bcl-2的表达上调，与未共培养的顺铂处理的NRK-52E细胞相比。因此，显示AD-MSC通过某些因子的分泌显着改善顺铂诱导的肾衰竭和肾小管细胞坏死，其随后抑制了体外的细胞凋亡途径。假设AD-MSC的分泌是由受损的肾小管细胞触发的。因此，AD-MSC由于其抗凋亡能力，对于肾损伤患者的治疗可能是重要的。