Protective effect of Allopurinol on renal injury in rats with chronic intermittent hypoxia
DU Yi1 LIANG-Shun2 WEI Yu-ting1 KE Jian-ting1 PEI Xue-feng1
1.Department of Nephrology,the Fifth Affiliated Hospital of Sun Yat-Sen University,Guangdong Province,Zhuhai 519000,China;
2.Department of Endocrinology,Yuebei People′s Hospital,Guangdong Province,Shaoguan 512000,China
Abstract： Objective To study the protective effect of allopurinol (ALLO) on renal injury in rats with chronic intermittent hypoxia (CIH).Methods A total of 40 male Wistar rats were randomly divided into the normal control group(10 rats) and the model group,the rats in the model group were divided into the model control group (10 rats),the low dose of ALLO group (20 mg/[kg·d],10 rats) and the high dose of ALLO group (40 mg/[kg·d],10 rats).The CIH mode was established in the model group,which were given gavage for 14 days.The levels of cystatin C (Cys-C) and vascular endothelial growth factor (VEGF) were measured in rats venous serum before and after treatment.The pathological changes of renal tissue were observed under light microscope.The expression of xanthine oxidase (XO) protein was detected by Western blot.The levels of superoxide dismutase (SOD),malondialdehyde (MDA) were detected by renal tissue homogenate.Results The serum Cys-C,VEGF levels and renal tissue MDA,XO expression level in the normal control group were higher than those in the model control group,the SOD level in the normal control group was lower than that in the model control group,the differences were statistically significant (P＜0.01).The serum Cys-C,VEGF levels and renal tissue MDA,XO expression levels of the model control group were higher than those of the low dose of ALLO group and the high dose of ALLO group after 2 weeks of modeling treatment,and renal tissue SOD level of the low dose of ALLO group was lower than that of the high dose of ALLO group (P＜0.01).The MDA level of the high dose of ALLO group was lower than that of the model control group and the low dose of ALLO group,and the SOD level of the high dose of ALLO group was higher than that of the model control group and the low dose of ALLO group (P＜0.05).There were no significant differences in the levels of serum CysC,VEGF,XO renal tissue expression between the high dose of ALLO group and the low dose of ALLO group (P＞0.05).Renal tissue MDA levels were correlated with serum VGEF (r=0.65,P<0.05).The renal HE staining in the model control group showed significant glomerular volume increase,glomerular mesangial cells and matrix hyperplasia,and some glomeruli showed focal segmental sclerosis.Vacuolar-like degeneration was found in renal tubular epithelial cells than in the high dose of ALLO group and the low dose of ALLO group.Conclusion Renal injury in CIH rats is associated with oxidative stress and VGEF.The effect of ALLO on oxidative stress in CIH rats is more significant with the increase of dose,which inhibits serum VGEF in CIH rats.ALLO attenuates renal injury in CIH rats through inhibition of oxidative stress response and VGEF.
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