Department of Nephrology, Zigong First People's Hospital, Zigong, Sichuan 643000, P.R. China.
Department of Imaging Medicine, Sichuan Vocational College of Health and Rehabilitation, Zigong, Sichuan 643000, P.R. China.
Int J Mol Med. 2021 Feb;47(2):511-522. doi: 10.3892/ijmm.2020.4805. Epub 2020 Dec 1.
Acute kidney injury (AKI) is characterized by an abrupt deterioration of renal function. Formononetin (FOR) protects against cisplatin (CIS)‑induced AKI, and it has various potential pharmacological and biological effects, including anti‑inflammatory, antioxidative and anti‑apoptotic effects. The current study investigated the role of FOR in CIS‑induced AKI. Rats were treated with CIS to establish an AKI model, followed by treatment with FOR. HK‑2 cells were treated with CIS, FOR, GW6471 [a peroxisome proliferator‑activated receptor α (PPARα) antagonist], eupatilin (a PPARα agonist) and nuclear factor erythroid 2‑related factor 2 (Nrf2) small interfering RNA (siNrf2), and cell proliferation and apoptosis were determined by MTT and flow cytometry assays. The mRNA and proteins levels of PPARα, Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were measured by reverse transcription‑quantitative PCR and western blotting. The results demonstrated that FOR attenuated the histopathological changes, the levels of blood urea nitrogen, creatinine, TNF‑α and IL‑1β, and the MDA content and MPO activity, whereas it enhanced CAT activity in the AKI rat model. Furthermore, FOR and eupatilin promoted cell viability and CAT activity, and increased the levels of PPARα, Nrf2 and HO‑1 and NQO1, but suppressed apoptosis and MPO activity, and reduced the levels of MDA, TNF‑α and IL‑1β in CIS‑treated HK‑2 cells. Notably, the aforementioned effects were reversed by GW6471 treatment or siNrf2 transfection. In conclusion, FOR protects against CIS‑induced AKI via activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.
急性肾损伤 (AKI) 的特征是肾功能突然恶化。芒柄花素 (FOR) 可预防顺铂 (CIS) 诱导的 AKI，其具有多种潜在的药理和生物学作用，包括抗炎、抗氧化和抗凋亡作用。本研究探讨了 FOR 在 CIS 诱导的 AKI 中的作用。大鼠用 CIS 处理以建立 AKI 模型，然后用 FOR 处理。用 CIS、FOR、GW6471（过氧化物酶体增殖物激活受体 α (PPARα) 拮抗剂）、朝鲜蓟素（PPARα 激动剂）和核因子红细胞 2 相关因子 2 (Nrf2) 小干扰 RNA (siNrf2) 处理 HK-2 细胞，并通过 MTT 和流式细胞术测定细胞增殖和凋亡。通过逆转录定量 PCR 和蛋白质印迹法测定 PPARα、Nrf2、血红素加氧酶-1 (HO-1) 和 NAD(P)H 醌氧化还原酶 1 (NQO1) 的 mRNA 和蛋白水平。结果表明，FOR 减轻 AKI 大鼠模型的组织病理学变化、血尿素氮、肌酐、TNF-α 和 IL-1β 水平以及 MDA 含量和 MPO 活性，同时增强 CAT 活性。此外，FOR 和朝鲜蓟素促进细胞活力和 CAT 活性，增加 PPARα、Nrf2、HO-1 和 NQO1 的水平，但抑制 CIS 处理的 HK-2 细胞中的凋亡和 MPO 活性，并降低 MDA、TNF-α 和 IL-1β 的水平。值得注意的是，GW6471 处理或 siNrf2 转染逆转了上述作用。总之，FOR 通过激活 PPARα/Nrf2/HO-1/NQO1 通路来保护 CIS 诱导的 AKI。
