Renmin Hospital of Wuhan University - Department of Urology - Wuhan, Hubei, China.
Acta Cir Bras. 2023 Aug 4;38:e382523. doi: 10.1590/acb382523. eCollection 2023.
To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model.
Rats were intraperitoneally injected with puerarin (50 or 100 mg/kg) per day for one week before renal I/R. The level of renal collagen deposition and interstitial fibrosis were observed by hematoxylin and eosin and Sirius Red staining, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemical staining. The ferroptosis related factors and TLR4/Nox4-pathway-associated proteins were detected by Western blotting.
Puerarin was observed to alleviate renal collagen deposition, interstitial fibrosis and the α-SMA expression induced by I/R. Superoxide dismutase (SOD) activities and glutathione (GSH) level were decreased in I/R and hypoxia/reoxygenation (H/R), whereas malondialdehyde (MDA) and Fe2+ level increased. However, puerarin reversed SOD, MDA, GSH and Fe2+ level changes induced by I/R and H/R. Besides, Western blot indicated that puerarin inhibited the expression of ferroptosis related factors in a dose-dependent manner, which further demonstrated that puerarin had the effect to attenuate ferroptosis. Moreover, the increased expression of TLR/Nox4-pathway-associated proteins were observed in I/R and H/R group, but puerarin alleviated the elevated TLR/Nox4 expression.
Our results suggested that puerarin inhibited oxidative stress and ferroptosis induced by I/R and, thus, delayed the progression of renal fibrosis, providing a new target for the treatment of renal fibrosis.
研究葛根素对肾缺血再灌注（I/R）模型中肾纤维化的作用及其机制。
在肾 I/R 前一周，每天通过腹腔注射给予大鼠葛根素（50 或 100mg/kg）。通过苏木精和伊红染色和天狼猩红染色观察肾胶原沉积和间质纤维化的程度，并通过免疫组织化学染色检查α-平滑肌肌动蛋白（α-SMA）的表达。通过 Western blot 检测铁死亡相关因子和 TLR4/Nox4 通路相关蛋白。
葛根素可减轻 I/R 引起的肾胶原沉积、间质纤维化和α-SMA 表达。超氧化物歧化酶（SOD）活性和谷胱甘肽（GSH）水平在 I/R 和缺氧/复氧（H/R）中降低，而丙二醛（MDA）和 Fe2+水平升高。然而，葛根素逆转了 I/R 和 H/R 引起的 SOD、MDA、GSH 和 Fe2+水平变化。此外，Western blot 表明，葛根素呈剂量依赖性抑制铁死亡相关因子的表达，进一步证明了葛根素具有减轻铁死亡的作用。此外，在 I/R 和 H/R 组中观察到 TLR/Nox4 通路相关蛋白的表达增加，但葛根素减轻了 TLR/Nox4 的表达升高。
我们的结果表明，葛根素抑制 I/R 引起的氧化应激和铁死亡，从而延缓肾纤维化的进展，为治疗肾纤维化提供了新的靶点。
