【摘要】 目的研究别嘌呤醇(ALLO)对慢性间歇性缺氧(CIH)大鼠肾损害的保护作用。方法将雄性Wistar大鼠40只随机分为正常对照组(10只)和模型组,模型组大鼠又分为模型对照组(10只)、ALLO小剂量组[20 mg/(kg·d),10只]、ALLO大剂量组[40 mg/(kg·d),10只]进行CIH模型造模,ALLO灌胃共14 d。治疗前后采取大鼠静脉血检测胱抑素C(Cys-C)、血管内皮生长因子(VEGF)水平,光镜下观察肾组织病理结构变化,采用Western blot检测黄嘌呤氧化酶(XO)蛋白表达,肾组织匀浆检测超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果模型对照组的血Cys-C、VEGF水平及肾组织MDA、XO表达水平高于正常对照组,SOD水平低于正常对照组,差异有统计学意义(P<0.01)。造模治疗2周后,模型对照组的血Cys-C、VEGF水平及肾组织MDA、XO表达水平高于ALLO小剂量组、ALLO大剂量组,SOD水平低于ALLO小剂量组、ALLO大剂量组(P<0.01)。ALLO大剂量组的MDA水平低于模型对照组及ALLO小剂量组,SOD水平高于模型对照组及ALLO小剂量组(P<0.05)。ALLO大剂量组与ALLO小剂量组的血Cys-C、VEGF水平,肾组织XO表达水平比较,差异无统计学意义(P>0.05)。肾组织的MDA水平与血VGEF有相关性(r=0.65,P<0.05)。模型对照组肾脏HE染色出现明显的肾小球体积增大,肾小球系膜细胞和基质增生,部分肾小球出现局灶性节段性硬化;肾小管上皮细胞可见空泡样变性,较ALLO大剂量组与ALLO小剂量组显著。结论 CIH大鼠的肾损伤与氧化应激及VGEF有关。ALLO对CIH大鼠的氧化应激反应有抑制作用且随剂量的增大作用更加显著,对CIH大鼠的血VGEF有抑制作用。ALLO可通过对氧化应激反应及VGEF的抑制减轻CIH大鼠的肾损伤。更多还原

【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.更多还原