急性缺血性肾损伤中IκB激酶β(IKKβ)的变化及其意义的初步研究
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国家自然科学基金资助项目(30670984)


The preliminary study about the changes and significance of IKKβ generated in renal acute ischemic injury
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    目的:通过建立大鼠肾脏急性缺血再灌注(I/R)及缺血预适应/再灌注(I/P+I/R)模型,初步研究不同的缺血方式后肾脏IκB激酶β(IKKβ)的变化及其与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的相互关系-方法:雄性SD大鼠摘除右肾-分离出左肾动脉后随机均分为3组:假手术组(sham组);缺血再灌注组(I/R组);缺血预适应+缺血再灌注组(I/P+I/R组)-分别用生化学检测血清肌酐(Scr)的变化,组织病理学评价肾小管损伤程度评分,用免疫荧光定量分析IKKβ的表达,免疫组织化学染色检测肾脏组织中NGAL的表达,免疫印迹检测肾脏组织中IKKβ-NGAL的表达-结果:Scr水平及肾小管损伤评分提示,I/R组肾脏组织病理改变明显,与sham组比较损伤程度重(P < 0.01);与I/R组比较,I/P+I/R组损伤程度则明显减轻(P < 0.05)-免疫荧光定量分析与免疫印迹检测IKKβ的表达提示,I/P+I/R组的表达明显高于sham组(P < 0.01,P < 0.05);I/R+I/P组较I/R组则明显减少(P < 0.05)-免疫组织化学染色检测与免疫印迹检测NGAL的表达提示,I/P+I/R组的表达明显高于sham组(P < 0.01,P < 0.05);I/R+I/P组较I/R组则明显减少(P < 0.05)-且IKKβ与NGAL两种蛋白的表达呈正相关(P <0.01)-结论:IKKβ参与了肾脏的缺血再灌注损伤,促进了肾损伤标志物NGAL的产生,肾脏缺血预适应抑制IKKβ的激活,减少NGAL的产生,与肾脏保护作用有关-

    Abstract:

    Objective:To establish modles of rat ischemia preconditioning(I/P) and ischemia reperfusion(I/R) and to study the changes of I kappB kinaseβ(IKKβ) and Neutrophil Gelatinase-Associated Lipocalin(NGAL). Method:Thirty male Sprague-Dawley rats were divided into 3 groups randomly after right kidney nephrectomy. Group A was sham-operated control. Group B rats were 45-minutes ischemic in the left renal artery while Group C rats were pretreatmented with 3 cycles of 2-minutes ischemia and 5-minutes reperfusion. All the rats were sacrificed at 24 h after reperfusion. We harvested kidneys and serum to do further analysis, including histological and functional parameters,expressions of NGAL and IKKβ in renal tissues. Results:Compared with rats suffered from ischemia-reperfusion injury, pretreatmented rats had a significant decrease in serum creatinine level and tubulointerstitial injury scores. In addition, expressions of IKKβ and NGAL at renal tubule were attenuated significantly. Moreover, our study showed IKKβ and NGAL were in positive correlation. Conclusion:IKKβ plays roles in renal ischemia-reperfusion injury ,give rise to the generation of NGAL. IKKβ inhibition in ischemia preconditioning attenuates renal injury and the espression of NGAL following acute ischemia-reperfusion injury

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武 煜,尹忠诚,曹长春,陈 宇,张立元,刘晓东,缪嘉燕.急性缺血性肾损伤中IκB激酶β(IKKβ)的变化及其意义的初步研究[J].南京医科大学学报(自然科学版),2009,29(4):454-458

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  • 收稿日期:2008-11-25
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