Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.
Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.
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Formononetin通过激活PPARα/NRF2/HO-1/NQO1通路对顺铂诱导的急性肾损伤具有保护作用。
DOI：
10.3892/ijmm.2020.4805
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发表时间：
2021-03
影响因子：
5.4
通讯作者：
Zhong Q
中科院分区：
文献类型：
--
作者：
Hao Y;Miao J;Liu W;Peng L;Chen Y;Zhong Q
急性肾损伤（阿基）的特征是肾功能突然恶化。芒柄花素（Formononetin，FOR）具有抗顺铂（cisplatin，CIS）诱导的急性肾损伤（AKI）的作用，具有抗炎、抗氧化、抗凋亡等多种药理学和生物学作用。本研究调查了FOR在CIS诱导的阿基中的作用。用CIS处理大鼠以建立阿基模型，随后用FOR处理。分别用CIS、FOR、GW 6471（过氧化物酶体增殖物激活受体α（PPARα）拮抗剂）、eupatilin（过氧化物酶体增殖物激活受体α激动剂）和核因子红细胞2相关因子2（Nrf 2）小干扰RNA（siNrf 2）处理HK-2细胞，MTT法和流式细胞术检测细胞增殖和凋亡。采用逆转录-定量PCR和蛋白质印迹法检测细胞中过氧化物酶体增殖物激活受体α（PPARα）、核转录因子2（Nrf 2）、血红素加氧酶-1（HO-1）和辅酶Ⅱ（NAD（P）H）醌脱氢酶-1（NQO 1）的mRNA和蛋白质水平。结果表明，FOR能减轻阿基大鼠的组织病理学改变，降低血尿素氮、肌酐、TNF-α、IL-1β水平，降低MDA含量和MPO活性，提高CAT活性。此外，FOR和eupatilin还能促进CIS处理的HK-2细胞的存活率和CAT活性，增加细胞内PPARα、Nrf 2、HO-1和NQO 1的水平，抑制细胞凋亡和MPO活性，降低MDA、TNF-α和IL-1β的水平。值得注意的是，上述作用被GW 6471处理或siNrf 2转染逆转。总之，FOR通过激活PPARα/Nrf 2/HO-1/NQO 1通路保护CIS诱导的阿基。
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.
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作者：
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DOI：
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