AIM; To establish a suitable animal model of nephropathy associated with metabolic syndrome (MS) induced by abnormal diet, and to investigate the effects of oxidalive stress on renal damage in MS rats. METHODS; Normal 7 -week -old male SD rats were randomly divided into 2 groups. The animals were fed with normal chow (control group, n = 10) or high - fat and high - salt diet plus 20% sucrose solution ( MS model group, n = 10) for 20 weeks. Systolic blood pressure (SBP) was measured monthly. The levels of blood glucose, serum and urinary creatinine (Cr) , total cholesterol (TC) , triglycerides (TG) , fasting insulin (Fins) , urinary protein, urinary albumin and urinary sodium were determined. Insulin resistance ( HOMA - IR), creatinine clearance ( Ccr) , urinary protein excretion ( UPE) , urinary albumin excretion (UAE) and urinary sodium excretion (USE) were calculated. Renal total -antioxidant capacity (T - AOC), inhibiting superoxide anion capacity (ISAC) , malondialdehyde (MDA) content, and antioxidant enzyme activity were measured. Renal protein expression of Cu/Zn - SOD, NADPH oxidase subunit P47pboxand p22pbox was detected by Western blotting. In addition, pathological changes of the kidney were observed with PAS and Masson staining,and degree of glomerulosclerosis (GS) and tubulointerstitial injury was evaluated. RESULTS; Compared with control rats, SBP, TC, TG, Fins, USE and UAE were increased in MS rats. Furthermore, the MS rats showed a significant elevation of renal MDA content, p47pbox protein expression and GS score, and reduction of T - AOC, ISAC, SOD activity, and Cu/Zn - SOD protein expression in the kidney. CONCLUSION; SD rats fed with abnormal diet produce a suitable animal model of MS nephropathy that mimics the major features of human MS. Oxidative stress caused by up - regulation of NADPH oxidase expression and down-regulation of SOD expression may be one of the mechanisms leading to MS renal damage.%目的:构建饮食诱导的代谢综合征(MS)肾病大鼠模型,并探讨氧化应激在肾脏损伤中的作用.方法:7周龄雄性SD大鼠随机分为正常对照组(n=10)和MS模型组(n=10).MS大鼠喂饲高脂高盐(HFS)饲料和20%蔗糖饮水20周.测定尾动脉收缩压(SBP);测空腹血糖(FBG)、血脂和胰岛素(FIns)水平,计算稳态胰岛素评价指数(HOMA-IR);测肌酐、尿蛋白、尿白蛋白和尿钠含量,并计算肌酐清除率(Ccr)、蛋白排泄率(UPE)、白蛋白排泄率(UAE)和钠排泄率(USE);测肾脏组织总抗氧化能力(T-AOC)、抑制超氧阴离子能力(ISAC)、丙二醛(MDA)含量以及抗氧化酶活性;Western blotting检测肾脏铜锌超氧化物歧化酶(Cu/Zn-SOD) 和NADPH氧化酶亚单位p47phox、p22phox蛋白表达;PAS和Masson染色观察肾脏病理变化并进行评分.结果:与正常组相比,MS大鼠SBP、血脂、FIns、HOMA-IR、USE和UAE增高;肾脏T-AOC、ISAC和SOD活性降低,MDA含量增加;p47phox蛋白表达增高,Cu/Zn-SOD蛋白表达降低;肾小球硬化评分升高.结论:喂饲大鼠HFS饮食和高糖饮水可建立模拟大部分临床特征的MS肾病模型.NADPH氧化酶表达增高和SOD表达减少而引起的氧化应激是导致MS大鼠肾脏损伤的机制之一.
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