诱导型一氧化氮合酶对二甲氧乙二酰甘氨酸预处理晚期肾保护作用的影响  

Delayed protective effects of dimethyloxallyl glycine preconditioning on the mouse kidney of ischemia reperfusion injury: Potential role of inducible nitric-oxide synthase

作　　者：陆文俊[1] 张晓丽[1] 叶志斌[1] 夏世金[2] 

机构地区：[1]复旦大学附属华东医院肾内科,上海市200040 [2]上海市老年医学研究所

出　　处：《实用老年医学》2013年第4期295-298,共4页Practical Geriatrics

基　　金：国家自然科学基金青年基金资助项目(81200494);上海市自然科学基金资助项目(11ZR1411700;12ZR1409400);上海市科委医学引导项目(124119a8700)

摘　　要：目的探讨脯氨酸羟化酶抑制剂二甲氧乙二酰甘氨酸(DMOG)预处理对小鼠肾缺血再灌注损伤(IRI)的晚期保护作用以及诱导型一氧化氮合酶(iNOS)在此过程中的作用。方法 24只雄性C57/BL小鼠随机分为4组:假手术(sham)组、IRI组、DMOG预处理组(DMOG+IRI)和GW274150干预组(GW274150+DMOG+IRI)。采用夹闭双侧肾蒂30min再灌注24h方法建立小鼠肾IRI模型。观察DMOG预处理及特异性iNOS抑制剂GW274150干预对小鼠肾功能、肾组织病理和细胞凋亡的影响;并应用Westernblot方法检测低氧诱导因子(HIF-1α)和iNOS蛋白的表达。结果 DMOG预处理组小鼠肾功能、肾组织病理学和肾组织细胞凋亡程度均较IRI组显著改善,GW274150干预可使以上作用明显减弱。结论 DMOG预处理对IRI产生晚期肾保护作用,iNOS抑制剂可削弱这种保护性影响,意味着iNOS参与了HIF-1α活化引发的晚期肾保护作用。Objective To demonstrate the possible role of prolyl hydroxylases inhibitor dimethyloxallyl glycine (DMOG) in inducing delayed preconditioning-like effects against ischemia reperfusion injury(IRI). Methods Mice were divided into four groups (n=6): sham group,IRI group, DMOG group(pretreated with DMOG 24 h before IRI) and GW274150+DMOG group(pretreated with DMOG followed by iNOS inhibitor GW274150 treatment 24 h before IRI). Renal function was reflected by blood serum creatinin (SCr). Morphologic changes were evaluated under light microscopy. Apoptosis in the kidney was detected by TUNEL staining. Hypoxia induced factor 1α(HIF-1α) and iNOS protein expressions were detected by Western blot. Results Renal function and histologic analysis showed improvement of tubulointerstitial injury due to ischemia by delayed preconditioning with DMOG. GW274150 antagonized the delayed renal protection afforded by DMOG. DMOG pretreated IRI kidney showed significantly higher expression of iNOS compared with sham group. The increase in iNOS expression was partially inhibited in animals treated by iNOS inhibitor GW274150 after DMOG pretreatment. Conclusions DMOG pretreatment induces delayed renal protection against IRI in mice and the beneficial effects are mitigated by pharmacological inhibition of iNOS, suggesting that the protective effects derived from HIF-1 activation via DMOG in the kidney are partially mediated by iNOS.

关 键 词：低氧诱导因子 肾脏 缺血再灌注 诱导型一氧化氮合酶 

分 类 号：R692.9[医药卫生—泌尿科学]