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人脐带间充质干细胞减轻顺铂诱导的急性和慢性肾损伤。

Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury.

机构信息

Centre for Clinical Laboratory of the Affiliated Hospital, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, P. R. China.

出版信息

Exp Biol Med (Maywood). 2013 Aug 1;238(8):960-70. doi: 10.1177/1535370213497176.

Abstract

Mesenchymal stem cell is becoming a promising candidate in acute kidney injury (AKI). We first reported that human umbilical cord mesenchymal stem cells (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but the role of hucMSCs in cisplatin-induced acute and chronic injury has been demonstrated. More specifically, it is still unknown whether hucMSCs halt renal interstitial fibrosis. In this study, we investigated the effect of hucMSCs in cisplatin-induced kidney injury and explored the mechanism of action. Blood urea nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs promoted renal cell regeneration, inhibited cell apoptosis, abrogated inflammatory responses and protected mitochondria. Moreover, Masson's trichrome staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC-treated rats at six and eight weeks after cisplatin injection. These results were corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and transforming growth factor β mRNA expression. Furthermore, hucMSCs prevented the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to the attenuation of chronic renal interstitial fibrosis. Taken together, our findings suggested that hucMSCs could decrease the kidney from development of later renal interstitial fibrosis by amelioration of early AKI.

摘要

间充质干细胞正在成为急性肾损伤 (AKI) 的有前途的候选者。我们首次报道了人脐带间充质干细胞 (hucMSCs) 可改善缺血/再灌注 AKI 大鼠的肾功能,但 hucMSCs 在顺铂诱导的急性和慢性损伤中的作用已得到证实。更具体地说,尚不清楚 hucMSCs 是否可以阻止肾间质纤维化。在这项研究中,我们研究了 hucMSCs 在顺铂诱导的肾损伤中的作用,并探讨了其作用机制。血液尿素氮 (BUN) 和肌酐 (Cr) 分析表明,在早期损伤时,hucMSC 治疗的大鼠的功能参数得到改善。hucMSCs 的移植促进了肾细胞的再生,抑制了细胞凋亡,减弱了炎症反应并保护了线粒体。此外,六和八周后注射顺铂,Masson 三色染色显示 hucMSC 治疗的大鼠肾脏组织中的纤维化水平降低。胶原沉积减少、Bax 与 Bcl-2 的比值和转化生长因子β mRNA 表达的降低证实了这一结果。此外,hucMSCs 可防止损伤的肾组织发生上皮间质转化 (EMT),从而减轻慢性肾间质纤维化。总之,我们的研究结果表明,hucMSCs 可通过改善早期 AKI 来减轻肾脏发生后期肾间质纤维化的程度。

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