降尿酸方对尿酸性肾病大鼠氧化损伤的影响OA

Objective To investigate the effects and mechanism of Jiangniaosuan Prescription regulating HACE1/Nrf2 signaling pathway in renal oxidative injury in rats with uric acid nephropathy.Methods A total of 40 8-week-old SPF male SD rats were randomly divided into normal group,model group,Jiangniaosuan Prescription group and allopurinol group,with 10 rats in each group.The normal group was given 1 mL/100 g of sterilized distilled water by gavage in the morning,and the other groups were given 1.5 g/kg of potassium oxyzinate combined with adenine 100 mg/kg in the morning,and 1 mL/100 g of sterilized distilled water in the normal group and model group in the afternoon,and Jiangniaosuan Prescription 16 g/kg and allopurinol 25 mg/kg in the treatment group,respectively,once a day,for consecutive 28 d.Serum and kidney tissue samples were collected,biochemical testing was performed to detect blood urea nitrogen(BUN),serum creatinine(SCr)and serum uric acid contents,the levels of glutathione(GSH)and superoxide dismutase(SOD)in serum were detected using kits,HE staining was used to observe the morphology of renal tissue,TUNEL staining was used to detect cell apoptosis,transmission electron microscopy was used to observe cell ultrastructure,Western blot was used to detect the expressions of containing HECT domain and anchor protein repeat sequence E3 ubiquitin ligase 1(HACE1),nuclear factor E2 related factor 2(Nrf2),Caspase-3 and Bax protein.Results Compared with the normal group,the contents of BUN,SCr and serum uric acid in the model group rats significantly increased(P<0.05),while the levels of GSH and SOD significantly decreased(P<0.05),with dilation of renal tubules,irregular lumen shape,local infiltration of lymphocytes,abundant urate crystals,mitochondrial condensation or swelling,shortened and disordered cristae,reduced number,and increased apoptosis of renal tubular epithelial cells,the expressions of HACE1 and Nrf2 proteins were significantly reduced(P<0.01),while the expressions of Caspase-3 and Bax proteins significantly increased(P<0.05).Compared with the model group,BUN,SCr and serum uric acid contents were significantly decreased in Jiangniaosuan Prescription group and allopurinol group(P<0.05,P<0.01),and the levels of GSH and SOD significantly increased(P<0.01),with reduced renal tissue damage,improved mitochondrial structure,decreased urate crystals,and decreased apoptosis of renal tubular epithelial cells,the expressions of HACE1 and Nrf2 proteins significantly increased,while the expressions of Caspase-3 and Bax proteins significantly decreased(P<0.05,P<0.01).Conclusion Jiangniaosuan Prescription can alleviate renal oxidative damage and tubular epithelial cell apoptosis in rats with uric acid nephropathy,and its mechanism may be related to the regulation of the HACE1/Nrf2 signaling pathway.