2022, Vol. 26 ›› Issue (23): 3609-3614

Asiaticoside protects the kidney from ischemia-reperfusion injury in a rat model by activating nuclear factor E2-related factor 2/hemeoxygenase-1 pathway

Zhu Shiyu1, Hu Yan1, Wang Suogang2, Lu Peng2, Wang Di2, Zhai Qiongyao2, Wang Guangce2   

Abstract: BACKGROUND: Prevention or reduction of kidney ischemia-reperfusion injury can improve the livability of kidney transplant. Therefore, it is necessary to develop safer, cheaper and more effective drugs to prevent or treat kidney ischemia-reperfusion injury.   
OBJECTIVE: To investigate the protective effect of asiaticoside on kideny ischemia-reperfusion injury in a rat model and its relevant mechanism.   
METHODS: A total of 40 Sprague-Dawley rats were randomly divided into four groups: sham surgery group, model group, asiaticoside group, and asiaticoside+brusatol group, with 10 rats in each group. The kidney pedicles were clamped for 45 minutes in the latter three groups to establish the rat kidney ischemia-reperfusion injury model. The rats in the asiaticoside and asiaticoside+brusatol groups were given asiaticoside suspension by gavage for 4 weeks in advance. Before modeling, the asiaticoside+brusatol group was given brusatol, a nuclear factor E2-related factor 2-specific inhibitor, by intraperitoneal injection for 5 continuous days. The levels of serum creatinine and urea nitrogen were detected. The expression of kidney injury molecule-1 in urine was detected by enzyme-linked immunosorbent assay. The expression levels of superoxide dismutase and malondialdehyde in kidney tissue were measured. Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue. The protein expression of nuclear factor E2-related factor 2 protein in kidney tissue was detected by immunohistochemistry. The protein expression of nuclear factor E2-related factor 2 and hemeoxygenase-1 protein in kidney tissue cells was detected by western blot assay.   
RESULTS AND CONCLUSION: Compared with the model group, the levels of serum creatinine and urea nitrogen and urinary kidney injury molecule 1 were significantly reduced in the asiaticoside group (all P < 0.05). Asiaticoside could also significantly increase the expression of superoxide dismutase (P < 0.05), decrease the expression of malondialdehyde in kidney tissue (P < 0.05), and improve the pathological changes of kidney tissue. Compared with the asiaticoside group, the combined use of asiaticoside and bruceol could increase the levels of serum creatinine and urea nitrogen, urinary kidney injury molecule 1, and malondialdehyde in the kidney tissue, while decrease the level of superoxide dismutase in the kidney tissue (all P < 0.05). Meanwhile, asiaticoside could significantly induce the translocation of nuclear factor E2-related factor 2, and increased the expression level of hemeoxygenase-1. Overall, these findings indicate that asiaticoside can protect against kidney ischemia-reperfusion injury by activating nuclear factor E2-related factor 2/hemeoxygenase-1 pathway.
Key words: asiaticoside, kidney, ischemia-reperfusion injury, brusatol, Nrf2/HO-1 pathway