Puerarin alleviated oxidative stress and ferroptosis during renal fibrosis induced by ischemia/reperfusion injury via TLR4/Nox4 pathway in rats

葛根素通过TLR4/Nox4通路减轻大鼠缺血/再灌注损伤诱发的肾脏纤维化过程中的氧化应激和铁死亡

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作者:Jun Jian, Dan Wang, Yufeng Xiong, Jingsong Wang, Qingyuan Zheng, Zhengyu Jiang, Jiacheng Zhong, Song Yang, Lei Wang

Conclusions

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.

Methods

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.

Purpose

To investigate the role of puerarin on renal fibrosis and the underlying mechanism in renal ischemia and reperfusion (I/R) model.

Results

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. Conclusions: 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.

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