Astragaloside IV protects against ischemia/reperfusion (I/R)-induced kidney injury based on the Keap1-Nrf2/ARE signaling pathway

作者：Su, Yanyan; Xu, Jiaqi; Chen, Siqi; Feng, Junxia; Li, Jingchun; Lei, Zihan; Qiao, Lingyan; Wang, Yaning^*; Zeng, Dewang^*

来源：Translational Andrology and Urology, 2022, 11(8): 1177-1188.

DOI：10.21037/tau-22-505

• Astragaloside IV
• acute kidney injury (AKI)
• chronic kidney injury
• keap1-Nrf2/ARE
• oxidative stress

Background: This study sought to investigate the protective effects of Astragaloside IV ( AS-IV) on ischemia-reperfusion (I/R) renal injury based on the keap1-Nrf2/ARE signaling pathway. @@@ Methods: A total of 36 male Sprague-Dawley rats (aged: 8 weeks; weighing: 200-220 g) were randomly divided into the following 6 groups (n=6 per group): (I) the control group; (II) the sham operation group; (III) the kidney I/R injury group (the I/R group); (IV) the kidney I/R injury group treated with 2 mg/kg of AS-IV (the low-dose group); (V) the kidney I/R injury group treated with 5 mg/kg of AS-IV (the mid-dose group); and (VI) the kidney I/R injury group treated with 10 mg/kg of AS-IV (the high-dose group). Serum creatinine (CRE), serum urea, malondialdehyde ( MDA), and superoxide dismutase ( SOD) were examined using enzyme-linked immunoassay kits. Cell apoptosis and the pathological damage to the renal tissue were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, and periodic acid-Schiff (PAS) staining. The immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blot methods were used to determine the expression of Nrf2, HO-1, Bcl-2 and Bax in the kidney tissue. @@@ Results: In the I/R rat model, the serum CRE level was increased. In the acute kidney injury (AKI) and chronic kidney disease (CKD) models, AS-IV treatment significantly decreased serum CRE levels in a dosedependent manner. AS-IV treatment also reduced the injury of renal tubular epithelial cells, increased the expression levels of Nrf2 and HO-1, decreased the rate of apoptosis, downregulated the level of MDA, and elevated the activity of SOD. In the CKD rat model, the AS-IV treatment groups had reduced renal tubular epithelial cell injury, increased expression levels of Nrf2 and HO-1, decreased MDA levels, and increased SOD activity compared to the I/R group. @@@ Conclusions: AS-IV induced the expression of Nrf2, enhanced the activity of antioxidant enzymes, reduced apoptosis, protected against renal I/R injury, and prevented AKI from transforming into CKD. These findings suggest that AS-IV is a promising drug for treating kidney injury.

• 单位
  南方医科大学; 1