Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Free Radic Res. 2021 Jul;55(7):842-852. doi: 10.1080/10715762.2021.1962008. Epub 2021 Sep 7.
The pathophysiology of septic acute kidney injury (AKI) is very complex and the fatality is high. Nrf2 is crucial for septic AKI, and dihydromyricetin (DMY) has a protective effect on LPS-induced AKI. We aimed to explore whether DMY could affect Nrf2 pathway by regulating miR-199b-3p and played a protective role in septic AKI. The mouse model was induced by cecal ligation and puncture (CLP) and the cell model was stimulated by LPS. Enzyme-linked immunosorbent assay was conducted to examine MDA, SOD, LDH, GSH, TNF-α, kidney injury molecule 1 (KIM-1), and IL-6 levels. The pathological changes were observed by hematoxylin-eosin staining. The targeted relationship between miR-199b-3p and Nrf2 was verified by a dual-luciferase reporter assay. Levels of SOD, GSH, NQO-1, Nrf2, and HO-1 were decreased, MDA, LDH, TNF-α, IL-6, and KIM-1, and miR-199b-3p were increased in the CLP group and LPS-induced HK-2 cells, while the effect was reversed after DMY treatment. There existed renal tubule cell edema and necrosis, inflammatory cell infiltration in the CLP group, the situation was partially improved by DMY. MiR-199b-3p bound to Nrf2. Nrf2 levels were increased, TNF-α, IL-6, and KIM-1 were decreased after transfected with miR-199b-3p inhibitor, these effects were reversed when co-transfected with si-Nrf2. TNF-α, IL-6, KIM-1, and miR-199b-3p levels were increased; Nrf2, NQO-1, and HO-1 levels were decreased in the LPS + DMY + mimics-miR group. MiR-199b-3p was increased in septic AKI models, DMY might alleviate septic AKI by regulating miR-199b-3p to affect the Nrf2 pathway.
脓毒症急性肾损伤（AKI）的病理生理学非常复杂，死亡率很高。Nrf2 对脓毒症 AKI 至关重要，二氢杨梅素（DMY）对 LPS 诱导的 AKI 具有保护作用。我们旨在探讨 DMY 是否可以通过调节 miR-199b-3p 影响 Nrf2 通路并在脓毒症 AKI 中发挥保护作用。通过盲肠结扎穿孔（CLP）诱导小鼠模型，通过 LPS 刺激细胞模型。通过酶联免疫吸附试验检测 MDA、SOD、LDH、GSH、TNF-α、肾损伤分子 1（KIM-1）和 IL-6 水平。苏木精-伊红染色观察病理变化。通过双荧光素酶报告基因实验验证 miR-199b-3p 与 Nrf2 的靶向关系。CLP 组和 LPS 诱导的 HK-2 细胞中 SOD、GSH、NQO-1、Nrf2 和 HO-1 水平降低，MDA、LDH、TNF-α、IL-6 和 KIM-1 以及 miR-199b-3p 水平升高，而 DMY 处理后则逆转了这种情况。CLP 组存在肾小管细胞水肿和坏死，炎性细胞浸润，DMY 部分改善了这种情况。miR-199b-3p 与 Nrf2 结合。转染 miR-199b-3p 抑制剂后 Nrf2 水平升高，TNF-α、IL-6 和 KIM-1 降低，当与 si-Nrf2 共转染时，这些作用被逆转。转染 LPS + DMY + mimics-miR 后，TNF-α、IL-6、KIM-1 和 miR-199b-3p 水平升高，Nrf2、NQO-1 和 HO-1 水平降低。脓毒症 AKI 模型中 miR-199b-3p 增加，DMY 可能通过调节 miR-199b-3p 影响 Nrf2 通路来减轻脓毒症 AKI。
