Study on the Protective Effect and Mechanism of Eriodictyol on Acute Renal Injury Induced by Sepsis in Rats
Objective:Explore the effect of Eriodictyol on acute kidney injury(SAKI)in rats with sepsis and elucidate its mechanism of action.Methods:A sepsis rat model was established using cecal ligation and perforation surgery.The successfully mod-eled rats were randomly divided into model group,low-dose Eriodictyol group,high-dose Eriodictyol group,and high-dose Eriod-ictyol+nuclear factor E2-related factor 2(Nrf2)inhibitor group,and sham surgery group was also established,10 rats in each group.Pre treatment with Eriodictyo and Nrf2 inhibitor was started 2 days before modeling,and continuous intervention for 3 days.24 hours after surgery,serum creatinine(Scr)and blood urea nitrogen(BUN)levels were measured using biochemical methods.The concentration of IL-1β and IL-6 in serum and levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in renal tissue were detected by ELISA.The change of renal histopathology was observed by HE staining.The reactive oxygen species(ROS)level in rat kidney tissue was detected by fluorescence probe staining.The protein expression levels of Nrf2 and Heme-oxygenase 1(HO-1)in rat kidney tissue were detected by Western blot.Results:Compared with the sham surgery group,the levels of Scr,Bun,IL-1β and IL-6 in serum of the model group rats were significantly increased(P<0.05),renal tissue injury was severe,renal tu-bular injury score was significantly increased(P<0.05),ROS levels in renal tissue were increased,SOD activity and Nrf2 and HO-1 protein expression levels were significantly reduced(P<0.05).Compared with the model group,there was no significant differ-ence in all indicators in the low-dose group of Eriodictyo(P>0.05).The levels of Scr,Bun,IL-1β and IL-6 in serum of the high-dose group of Eriodictyo were significantly reduced(P<0.05),renal tissue damage was alleviated,renal tubular injury score was significantly reduced(P<0.05),ROS levels in renal tissue were reduced,SOD activity and Nrf2 and HO-1 protein expression levels were significantly increased(P<0.05).Nrf2 inhibitor reversed the inhibitory effect of high-dose Eriodictyo on oxidative stress and inflammatory response in SAKI rats(P<0.05).Conclusion:Eriodictyo pretreatment can inhibit oxidative stress and in-flammation levels in sepsis acute kidney injury rats,alleviate kidney damage,and its mechanism of action is related to the activation of Nrf2/HO-1 signaling pathway.
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