Yoshida Takuya, Kumagai Hiromichi, Kohsaka Tetsuya, Ikegaya Naoki
Department of Clinical Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
Nephron Exp Nephrol. 2014;128(1-2):9-20. doi: 10.1159/000365852. Epub 2014 Nov 11.
Cisplatin (CDDP)-induced acute kidney injury (AKI) involves pro-inflammatory responses, apoptosis of renal tubular epithelial cells and vascular damage. AKI increases the risk of chronic kidney disease. Relaxin (RLX) has anti-apoptotic and anti-fibrosis properties. The aim of this study was to investigate the effects of RLX on CDDP-induced nephrotoxicity.
We investigated the mitigating effects of RLX based on the etiopathology of AKI induced by CDDP, and also the anti-fibrotic effect of RLX on renal fibrosis after AKI. In the short-term experiments, rats were divided into the control group, CDDP group, and CDDP+RLX group. In the latter group, RLX was infused for 5 or 14 days using an implanted osmotic minipump. CDDP was injected intraperitoneally (6 mg/kg) after RLX or saline infusion. At 5 and 14 days post-CDDP, the kidneys were removed for analysis. The effect of RLX on renal fibrosis after AKI was evaluated at 6 weeks post-CDDP.
In short-term experiments, CDDP transiently increased plasma creatinine and blood urea nitrogen with peaks at day 5, and RLX prevented such rises. Semiquantitative analysis of the histological lesions indicated marked structural damage and apoptotic cells in the CDDP group, with the lesions being reduced by RLX treatment. Overexpression of Bax, interleukin-6 and tumor necrosis factor-α observed in the kidneys of the CDDP group was reduced in the CDDP+RLX group. In the long-term experiments, RLX significantly reduced renal fibrosis compared with the CDDP group.
The results suggested that RLX provided protection against CDDP-induced AKI and subsequent fibrosis by reducing apoptosis and inflammation.
顺铂（CDDP）诱导的急性肾损伤（AKI）涉及促炎反应、肾小管上皮细胞凋亡和血管损伤。AKI会增加慢性肾脏病的风险。松弛素（RLX）具有抗凋亡和抗纤维化特性。本研究旨在探讨RLX对CDDP诱导的肾毒性的影响。
我们基于CDDP诱导的AKI的病因病理研究了RLX的减轻作用，以及RLX对AKI后肾纤维化的抗纤维化作用。在短期实验中，将大鼠分为对照组、CDDP组和CDDP+RLX组。在后者组中，使用植入式渗透微型泵输注RLX 5天或14天。在输注RLX或生理盐水后腹腔注射CDDP（6 mg/kg）。在CDDP注射后第5天和第14天，取出肾脏进行分析。在CDDP注射后6周评估RLX对AKI后肾纤维化的影响。
在短期实验中，CDDP使血浆肌酐和血尿素氮短暂升高，在第5天达到峰值，而RLX可防止这种升高。组织学损伤的半定量分析表明，CDDP组有明显的结构损伤和凋亡细胞，RLX治疗可减轻这些损伤。CDDP组肾脏中观察到的Bax、白细胞介素-6和肿瘤坏死因子-α的过表达在CDDP+RLX组中降低。在长期实验中，与CDDP组相比，RLX显著减少了肾纤维化。
结果表明，RLX通过减少细胞凋亡和炎症，对CDDP诱导的AKI及随后的纤维化提供保护。
