Abstract:

Objective To discuss the ameliorative effect of total flavonoids from corn silk （TFCS） on kidney injury in the rats with urate nephropathy， and to clarify the possible mechanism. Methods Sixty male Wistar rats were randomly divided into control group， model group， positive control group ［benzbromarone（BZM） group， 5 mg·kg^-1·d^-1］， low dose of TFCS group （20 mg·kg^-1·d^-1）， medium dose of TFCS group （40 mg·kg^-1·d^-1）， and high dose of TFCS group （80 mg·kg^-1·d^-1）， and there were 10 rats in each group. Except for control group， the rats in the other groups were administered potassium oxonate （350 mg·kg^-1） and adenine （70 mg·kg^-1） by gavage for 4 weeks to establish the hyperuricemic nephropthy models. The rats in different doses of TFCS groups were treated with TFCS for 2 weeks. Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated； HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay（ELISA） method was used to detect the levels of uric acid （UA）， creatinine （Cr）， blood urea nitrogen （BUN）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum and levels of β2-microglobulin （β₂-MG） and microalbumin （ALB） in the urine of the rats in various groups； Western blotting method was used to detect the expression levels of urate transporter 1 （URAT1）， glucose transporter 9 （GLUT9）， and ATP-binding cassette transporter G2 （ABCG2） proteins in kidney tissue of the rats in various groups. Results Compared with control group， the renal blood perfusion volume of the rats in model group was significantly decreased （P<0.01）. Compared with model group， the renal blood perfusion volumes of the rats in BZM group and low， medium， and high doses of TFCS groups were significantly increased （P<0.05 or P<0.01）. Compared with control group， the kidney weight of the rats in model group was increased， with visible white granular spots on the surface， absence of blood color， and kidney volume was increased. Compared with model group， the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased， with color tending toward that in control group， and the white granular spots on the surface were significantly reduced. Compared with model group， the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased （P<0.01）. The HE staining results showed there were no abnormalities in kidney tissue structure in control group， while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group； compared with model group， the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups. The Masson staining results revealed no obvious collagen fiber deposition in control group， whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group， and the collagen volume fraction （CVF） was increased compared with control group （P<0.01）； compared with model group， the CVFs of the rats in BZM group and different doses of TFCS groups were decreased （P<0.01）. The ELISA results showed that compared with control group， the levels of UA， Cr， BUN， IL-6， and TNF-α in serum of the rats in model group were increased （P<0.01）； compared with model group， the levels of UA， Cr， BUN， IL-6， and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased （P<0.01）. Compared with control group， the levels of β₂-MG and ALB in urinary in model group were increased （P<0.01）； compared with model group， the levels of β₂-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased （P<0.05 or P<0.01）. The Western blotting results showed that compared with control group， the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased （P<0.01）， while the expression level of ABCG2 protein was decreased （P<0.01）. Compared with model group， the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased （P<0.05 or P<0.01）， and the expression level of ABCG2 protein was increased （P<0.01）. Conclusion TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model， and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

Key words: Extract of total flavonoids from corn silk, Urate nephropathy, Blood perfusion, Uric acid transporter, Kidney injury