The renoprotective effect of curcumin against cisplatin-induced acute kidney injury in mice: involvement of miR-181a/PTEN axis
The renoprotective effect of curcumin against cisplatin-induced acute kidney injury in mice: involvement of miR-181a/PTEN axis
复制标题
姜黄素对顺铂诱导的小鼠急性肾损伤的肾脏保护作用：miR-181a/PTEN轴的参与
DOI：
10.1080/0886022x.2020.1751658
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发表时间：
2020-01-01
期刊：
影响因子：
3
通讯作者：
Gong, Quan
中科院分区：
文献类型：
--
作者：
Huang, Si-Jia;Huang, Jing;Gong, Quan
背景：肾毒性，尤其是急性肾损伤（AKI），是顺铂主要的剂量限制性毒性。尽管近期研究表明姜黄素能有效预防顺铂诱导的AKI，但仍需进一步研究以了解其机制。
方法：我们建立了一个AKI小鼠模型。将雄性C57BL/6小鼠分为三组：生理盐水组（对照）、顺铂组（CP）和姜黄素 + 顺铂组（CP + Cur）。CP组接受单次腹腔内（i.p.）注射顺铂，而对照组接受生理盐水。CP + Cur组在顺铂注射前3天接受腹腔内姜黄素注射，并在之后继续注射姜黄素3天，直至安乐死的前一天。通过血清学和组织学分析评估肾损伤。采用蛋白质印迹法和实时定量聚合酶链反应（qRT - PCR）检测肾组织中磷酸酶和张力蛋白同源物（PTEN）以及微小RNA（miR）-181a的表达。生物信息学预测和蛋白质印迹法在体外验证了miR - 181a的靶标。
结果：姜黄素治疗减轻了顺铂诱导的肾毒性，这通过血尿素氮（BUN）值以及肾脏的组织学分析得到验证。在分子水平上，姜黄素治疗降低了顺铂诱导的miR - 181a表达水平，并恢复了顺铂抑制的体内PTEN表达。我们在培养的人胚胎肾293T细胞中验证了miR - 181a对PTEN的直接调控。
结论：我们表明miR - 181a/PTEN轴参与了姜黄素对顺铂诱导的AKI的肾保护作用，并为姜黄素减轻顺铂诱导的肾毒性的能力提供了新的证据。
Abstract Background Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required. Methods We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro. Results Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells. Conclusions We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity.