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作 者:丁巍[1] 黄松明[1] 张爱华[1] 朱春华[2] 陈秋霞[2] 冯泉城[2] 郭梅[2] 潘晓勤[2] 费莉[2]
机构地区:[1]南京医科大学附属南京儿童医院肾脏科,江苏南京210008 [2]南京医科大学儿科医学研究所,江苏南京210029
出 处:《南京医科大学学报(自然科学版)》2009年第3期350-355,405,共7页Journal of Nanjing Medical University(Natural Sciences)
基 金:江苏省社会发展项目(BS2007015);南京市科技发展计划(200702082)
摘 要:目的:探讨迷迭香酸对小鼠单侧输尿管梗阻(UUO)模型肾间质纤维化的抗氧化保护作用。方法:将雄性C57BL/6J小鼠随机分成3组:假手术对照组(Sham组,n=8)、UUO模型组(结扎左侧输尿管制作UUO模型,n=24)、UUO迷迭香酸干预组(UUO+RA组,n=24)。除Sham组外,其余2组根据不同的观察时间细分为3、7、14天亚组(n=8)。术后第3、7、14天分别处死各组小鼠,组织病理学方法观察肾小管间质损伤情况;Western blotting方法检测肾组织中波形蛋白(Vimentin)和E-钙黏蛋白(E-cadherin)表达;比色法测定小鼠左肾皮质匀浆中脂质过氧化标志物MDA以及抗氧化酶SOD的含量。结果:UUO模型组与假手术组比较:随着模型损伤时间的延长,肾间质损伤程度逐渐加重,Vimentin和MDA含量明显增高,E-cadherin和SOD含量明显降低。迷迭香酸干预组与UUO模型组比较:3天时肾脏病理、Vimentin、E-cadherin以及MDA、SOD含量无明显改变;7天时肾间质纤维化减轻,Vimentin、MDA含量降低,E-cadherin、SOD含量增高;14天时肾间质纤维化明显减轻,Vimentin、MDA含量明显降低,E-cadherin、SOD含量明显增高。结论:迷迭香酸可能通过减少单侧输尿管梗阻侧肾皮质脂质过氧化物的产生、增加抗氧化酶的含量,从而改善小鼠氧化应激所致的肾间质纤维化。Objective:To investigate the antioxidative effect of Rosmarinic acid on kidney of mice with unilateral ureteral obstruction (UUO). Methods:Male C57BL/6J mice were randomly divided into 3 groups:Sham-operated group (n = 8), UUO model group (UUO model was established by ligating the left ureter, n = 24) and UUO+RA group(UUO model mice were treated with RA, n = 24). The latter 2 groups were divided into 3 subgroups according to times(3d, 7d and 14d) after intervention(n = 8). Mice underwent UUO were killed at 3, 7, 14 days. The time course of injurious process in mice with UUO were examined by histopathology; Western Blotting of Vimentin as well as E-cadherin were measured; Malondialdehyde(MDA), superoxide dismutase(SOD) contents in the homogenized lysate of obstructive renal cortex were determined. Results: Compared with those in Sham-operated group, from 3 to 14 day, injury of renal interstitum exacerbated gradually in UUO model group, Vimentin and MDA increased significantly, E-cadherin and SOD decreased significantly. Compared with those in UUO model group, Vimentin, E-cadherin, SOD and MDA showed no significant difference in UUO+RA group on 3d; Vimentin and MDA decreased, E-cadherin and SOD increased, renal interstitial fibrosis attenuated in UUO+ RA group on 7d, till 14d. Conclusion:Rosmarinic acid may attenuated renal interstitial fibrosis in mice underwent UUO by reducing lipid peroxidation production and improving antioxidative enzyme contents.
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