Wu Zhen, Li Chunfeng, Li Qiang, Li Jing, Lu Xin
Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Blood Transfusion, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Exp Ther Med. 2020 Oct;20(4):3122-3129. doi: 10.3892/etm.2020.9081. Epub 2020 Jul 29.
Cisplatin (DDP) is a commonly used chemotherapy drug; however, the side effects associated with its use, particularly acute kidney injury (AKI), limit its clinical application. Puerarin is a natural flavonoid extracted from the Chinese medical herb , which has been reported to alleviate DDP-induced nephrotoxicity. However, the mechanisms underlying puerarin regulation on microRNA (miR)-31-mediated signaling pathways in AKI remain unknown. Thus, the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that DDP upregulated the levels of miR-31 in a concentration-dependent manner, both and . Furthermore, DDP significantly increased blood urea nitrogen and malondialdehyde content, serum creatinine and histopathological changes, while significantly decreasing the expression levels of superoxide dismutase, catalase and glutathione S-transferase in kidney tissues. TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway, which is downstream of miR-31. The effects induced by DDP were counteracted following treatment with puerarin. Taken together, the results of the present study suggest that puerarin exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway.
顺铂(DDP)是一种常用的化疗药物;然而,其使用所带来的副作用,尤其是急性肾损伤(AKI),限制了它的临床应用。葛根素是从中药材中提取的一种天然黄酮类化合物,据报道它可以减轻顺铂诱导的肾毒性。然而,葛根素对急性肾损伤中微小RNA(miR)-31介导的信号通路的调控机制仍不清楚。因此,本研究旨在通过逆转录-定量聚合酶链反应和蛋白质免疫印迹分析,研究葛根素在顺铂诱导的急性肾损伤大鼠模型中的作用。结果表明,顺铂以浓度依赖的方式上调miR-31的水平,无论是在体内还是体外。此外,顺铂显著增加血尿素氮和丙二醛含量、血清肌酐和组织病理学变化,同时显著降低肾组织中超氧化物歧化酶、过氧化氢酶和谷胱甘肽S-转移酶的表达水平。TUNEL和蛋白质免疫印迹分析表明,顺铂增加凋亡蛋白的表达水平并影响miR-31下游的Numb/Notch1信号通路。用葛根素治疗后,顺铂诱导的效应被抵消。综上所述,本研究结果表明,葛根素通过上调miR-31表达并抑制Numb/Notch1信号通路,对顺铂诱导的急性肾损伤具有肾脏保护作用。