Fisetin attenuates diabetic nephropathy by regulating transcriptional coactivator p300 and matrix metalloproteinase-2 / 中华内分泌代谢杂志

ABSTRACT

Rat models of diabetes were established by injecting streptozocin intraperitoneally.According to random number table,three groups were dividednormal group,diabetic group,and fisetin-treated group.After 24 weeks,all rats were sacrificed.Biochemical parameters of blood and urine samples were tested.The pathological changes were observed by paraffin sections staining with HE.The expression of extracellular matrix proteins was analyzed via PAS and Masson staining.Location of p300 protein expression was analyzed by immunohistochemistry.The protein expressions of p300 and MMP-2 were determined by Western blotting.The mRNA expressions of MMP-2 were analyzed via real-time PCR.The biochemical parameters and kidney pathological images in fisetin-treated group were better than those in diabetic group.The expression of extraeellular matrix proteins was lower than that in diabetic group.Immunohistochemistry analysis showed that among three groups the expression of p300 was mainly in glomeruli,and was also expressed in cell nucleus and cytoplasm and the coloration of fisetin-treated group was weakened as compared with diabetic group.Western blotting analysis showed that the expression of p300 protein in fisetin-treated group was lower than that in diabetic group(P＜O.05).The expressions of MMP-2 mRNA and MMP-2 protein were higher than those in diabetic group (P ＜ 0.05).It is suggested that fisetin may attenuate diabetes associated abnormalities in the kidney of rats,owing probably to inhibiting the expressions of p300 and enhancing the expressions of MMP-2.