Objective: To investigate the protective effect of rhubarb extract on acute kidney injury and the effect of Keap1/Nrf2 signaling pathway in sepsis rats. Methods: The Sepsis rat model of acute kidney injury was established and the rats were randomly divided into 5 groups:Control group,AKI group,AKI+RE 50 mg·kg-1 group,AKI+RE 100 mg·kg-1 group and AKI+RE 200 mg·kg-1 group for follow-up experiments. Serum creatinine and urea nitrogen were measured by automatic biochemical analyzer. 24 h urine protein was detected by quantitative test box. HE staining was used to detect the degree of pathological damage of renal tissues. Apoptosis of renal tissue was detected by TUNEL staining. The contents of F4/80+iNOS+ and F4/80+IL-10+ in peripheral blood were detected by flow cytometry. TNF-α and IL-6 in peripheral blood were detected by ELISA. The expression levels of Caspase-3, cleaved Caspase-3,Bax,Bcl-2,Keap1,Nrf2,p-Nrf2 and HO-1 were detected by western blotting. Results: The results showed as follows:compared with Control group,the levels of 24 h urine protein,serum creatinine and urea nitrogen in AKI group were significantly increased（P<0.05）,the cell apoptosis rate was significantly increased（P<0.05）,and the ratios of cleaved Caspase-3/Caspase-3 and Bax/Bcl-2 were significantly increased（P<0.05）. The contents of F4/80+iNOS+ and F4/80+IL-10+ were significantly increased（P<0.05）,the contents of TNF-α and IL-6 were significantly increased（P<0.05）,the protein levels of KEAP1 and HO-1 and the p-Nrf2/Nrf2 ratio were significantly decreased（P<0.05）. Compared with AKI group,the levels of 24 h urine protein,serum creatinine and urea nitrogen in AKI+Re 100 and 200 mg·kg-1 groups were significantly decreased（P<0.05）,the degree of pathological injury was significantly improved,and the rate of apoptosis was significantly decreased（P<0.05）. The cleaved Caspase-3/Caspase-3,Bax/Bcl-2 ratio were significantly decreased（P<0.05）,the content of F4/80+iNOS+ was significantly decreased（P<0.05）,and the content of F4/80+IL-10+ was significantly increased（P<0.05）. The contents of TNF-α and IL-6 were significantly decreased（P<0.05）,the protein levels of KEAP1 and HO-1 and the p-Nrf2/Nrf2 ratio were significantly increased（P<0.05）. Conclusion: Rhubarb extract can improve renal injury by mediating Keap1/Nrf2 signaling pathway,inhibit renal cell apoptosis and release of inflammatory factors, and have protective effects on sepsis rat model of acute renal injury .
JIA He-lei, LU Chang-qing, YUAN Bin, LIU Han-yang, WANG Teng-fei
. Protective effect of rhubarb extract on acute kidney injury and its effect on Keap1/Nrf2 signaling pathway in sepsis rats*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(6)
: 979
-985
.
DOI: 10.16155/j.0254-1793.2021.06.06
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