摘要
目的1.探讨氧化应激在血管紧张素Ⅱ(AngⅡ)诱导的蛋白尿和肾小球足细胞损伤中的作用;2.观察过氧化物酶体增殖物活化受体γ(PPARγ)激动剂罗格列酮对AngⅡ诱导的蛋白尿和肾小球足细胞损伤的抑制作用。方法雄性C57BL/6小鼠24只随机分为:健康对照组、AngⅡ模型组、Tempol治疗组和罗格列酮治疗组。尿8-isoprostane和清蛋白采用酶联免疫吸附试验(ELISA)检测;应用透射电镜观察肾小球足细胞损伤;实时定量聚合酶链式反应(RT-PCR)检测肾组织中nephrin和podocin表达。结果1.AngⅡ灌注后尿中8-isoprostane和清蛋白排泄分别是健康对照组的5.45倍和16.65倍;肾小球足细胞出现广泛足突融合;肾组织中nephrin和podocin表达显著降低,分别是健康对照组的56%和49%。2.Tempol治疗后尿8-isoporstane和清蛋白排泄分别降低68%和77%;肾小球足细胞损伤明显减轻;肾组织中nephrin和podocin表达显著增加,分别是模型组的1.43倍和1.51倍。3.罗格列酮治疗后尿中8-isoprostane和清蛋白排泄分别降低57%和74%;AngⅡ诱导的肾小球足细胞损伤在罗格列酮治疗后明显好转;肾组织中nephrin和podocin表达亦显著增加,是模型组的2.05倍和1.58倍。结论AngⅡ通过诱导氧化应激而导致蛋白尿和肾小球足细胞损伤;PPARγ激动剂通过抑制氧化应激阻断AngⅡ诱导的蛋白尿和肾小球足细胞损伤。
Objective 1, To explore the role of oxitave stress on angiotensin Ⅱ （ Ang Ⅱ ） - induced podocyte injury in mice;2, To investigate the inhibitory effect of peroxisome proliferator -activated receptor- γ （PPAR γ） agonist rosiglitazone on Ang Ⅱ -induced podocyte injury, Methods Twenty - four male mice were randomly divided into four groups ： nomal control, Ang Ⅱ infusion, Tempol treatment and Rosiglitazone treatment group. Urinary albumin and 8 -isoprotane excretion were measured by enzymelinked immunosorbent assay（EIJSA）. Renal podocyte injury was evaluated by transmission electronic microscopy. Nephrin and podocin gcne expression was determined by real time polymerase chain reaction. Results 1, Ang Ⅱ infusion increased urinary 8 - isoprostane and albumin excretion by 5, 45 - and 16, 65 - fold, respectively. Ang Ⅱ induced podocyte injury, and decreased nephrin and podocin expression by 56% and 49% , respectively. 2, Tempol administration significantly decreased Ang Ⅱ - induced urinary 8 - isoprostane and albumin excretion by 68% and 77%, Podocyte injury was restored, and neprhin and podocin expression increased by 1.43 - and 1.51 -fold, respectively. 3, PPAR γ agonist rosiglitazone significantly inhibited Ang Ⅱ - induced urinary 8 - isoprostane and albumin excretion by 57% and 74% ,respectively. Podocyte injury was also blunted, and neprhin and podocin expression increased by 2.05 - and 1.58 -fold, respectively, compared with Ang Ⅱ infusion group. Conclusions Ang Ⅱ induced proteinuria and podocyte injury via oxidative stress;PPAR γ ligand rosiglitazone blocked Ang Ⅱ -induced proteinuria and pedocyte injury via inhibition of oxidative stress.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2007年第22期1734-1736,共3页
Journal of Applied Clinical Pediatrics
基金
国家自然科学基金项目资助(30100081)
江苏省自然科学基金项目资助(BK2004144
BK2007259)
江苏省社会发展基金项目资助(BS2003050)
