LI Lan 1 , CHENG Dongqi 1 C , YUAN Yujia 1 , ZHONG Ling 2 , ZHAO Kun 1 , AN Xingxing 1 , LIU Jingping 1 , CHEN Younan 1 , LU Yanrong 1
  • 1. Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
  • 2. Department of Clinical Laboratory, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, P. R. China;
YUAN Yujia, Email: 766718155@qq.com
Hyperuricemic nephropathy; Renal injury; Potassium oxanate; Adenine; Rats
10.7507/1002-0179.202001197
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Objective To explore the optimal conditions of rat model of hyperuricemia (HUA) induced by different doses of potassium oxanate (PO) combined with adenine, and to provide reference for the treatment of HUA.Methods Male Sprague-Dawley rats (220-240 g body weight) were divided into normal control group, potassium oxanate (1000, 1500 mg/kg) and adenine (0, 50, 100 mg/kg) combined model groups, with 8 rats in each group. After 5 weeks of intragastric administration, blood were collected from tail vein of rats every week, and serum uric acid, creatinine and blood urea nitrogen level were measured. At the 6th week, the changes of the pathological characteristics, expression of inflammatory and fibrosis-related factors in the kidneys were observed.Results In the 1500 mg/kg potassium oxanate combined with 100 mg/kg adenine group, rats died after 2 weeks of molding, and the survival rate at the 6th week was 62.5%; but there was no significant difference between the other groups and the normal control group in survival rate (P>0.05). Compared with the normal group, the level of serum uric acid in each model group increased significantly after 1 week of molding (P<0.05), but recovered to the pre-model level after stopping intragastric administration in week 6. After 5 weeks, in model groups the levels of serum creatinine and blood urea nitrogen were higher than those in the normal control group; and the inflammation and fibrosis-related factors mRNA and protein expression of kidney tissue in model groups increased with the increase of ademine dose, and there was a significant difference in the PO 1 000 mg/kg with adenine 100 mg/kg group, PO 1 500 mg/kg with Adenine 50 mg/kg group compared to the normal control group (P<0.05). The results of renal anatomy and histology testing in rats showed that with the increased of the dosage of PO and adenine in the model groups, the increase of white deposition of renal medulla, tubulointerstitial fibrosis, and tubular epithelial cell necrosis was found, and the glomerular atrophy aggravated. Compared with the indexes in the normal control group, the expression levels of inflammation and fibrosis related genes and proteins in the 50 mg/kg adenine combined with 1 500 mg/kg PO group were higher, and inflammatory cell infiltration and fibrosis were observed, which was consistent with the clinical manifestation of hyperuricemia induced renal injury.Conclusion PO (1500 mg/kg) combined with adenine (50 mg/kg) can establish a stable hyperuricemic nephropathy model in rats.

Citation： LI Lan, CHENG Dongqi, YUAN Yujia, ZHONG Ling, ZHAO Kun, AN Xingxing, LIU Jingping, CHEN Younan, LU Yanrong. Establishment and evaluation of hyperuricemic nephropathy model induced by different doses of potassium oxanate combined with adenine in rats. West China Medical Journal, 2021, 36(5): 643-650. doi: 10.7507/1002-0179.202001197 Copy

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