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IKKα影响小鼠缺血性肾损伤的修复 被引量:1

The effect of IKKα on the repair phase of ischemic renal injury in mice
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摘要 目的:研究IκB激酶α(IκB kinaseα,IKKα)对缺血再灌注(ischemia-reperfusion,IR)肾损伤恢复期小鼠炎细胞浸润及炎症介质表达的影响。方法:将C57BL/6小鼠分为假手术组、IR组、干扰组、干扰对照组。干扰组及干扰对照组提前2周给予肾实质注射慢病毒,双侧肾蒂夹闭20 min后再灌注3 d建立动物模型,假手术组仅分离肾蒂,不予夹闭。通过血肌酐、尿素氮水平和HE染色评价肾功能及组织形态学改变,免疫组织化学方法检测巨噬细胞浸润及细胞增殖情况,并通过Western blot检测IKKα、p-IKKα、肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-18、IL-1β蛋白的表达。结果:与IR组和干扰对照组相比,IKKα干扰组血肌酐和尿素氮显著增高(P<0.05),肾组织病理损害较重,细胞增殖明显降低(P<0.05);巨噬细胞浸润及炎症介质TNF-α、IL-18、IL-1β的表达增多(P<0.05)。结论:IKKα的表达影响并且促进了肾脏缺血再灌注损伤的修复。 Objective:To investigate the effect of IKKα on inflammatory cell infiltration and the expression of inflammatory mediators in the repair phase of ischemia-reperfusion (IR)renal injury in mice. Methods:C57BL/6 mice were divided into 4 groups, including the Sham group,the IR group,the interference group and the control of interference group. The interference group and interference control group were injected with lentivirus in renal two weeks ago. The bilateral renal pedicle was occluded for 20 rain and then with reperfusion of 3 days to establish IR renal injury model. The sham group only separated bilateral renal pedicle without clipping. Serum creatinine, blood urea nitrogen and HE staining were preformed to evaluate renal function and morphological changes. The macrophages (F4/80+)infihration and proliferation factor Ki67 expression were detected by immunohistochemical detection, and the distribution and the expressions of IKKα, p-IKKα and inflammation mediators tumor necrosis factor-α(TNF-α),interleukin-18 (IL- 18) and IL-1β were detected by Western blot. Results:Compared to the control of interference group and the IR group,the serum creatinine and blood urea nitrogen of the interference group was significantly higher (P 〈 0.05)and renal pathological damage was severer. The cell proliferation factor Ki67 expression was significantly decreased in the interference group (P 〈 0.05); the infiltration of macrophage and the expression of inflammatory mediators of TNF-α IL-18 and IL-1α were increased (P 〈 0.05). Conclusion: The expression of IKKα has effect and promote the repair of renal ischemia-reperfusion injury.
出处 《南京医科大学学报(自然科学版)》 CAS CSCD 北大核心 2013年第5期610-615,共6页 Journal of Nanjing Medical University(Natural Sciences)
基金 国家自然科学基金(81170658)
关键词 IKKα 肾脏 缺血再灌注 修复 IκB kinase α renal ischemia-reperfusion repair
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参考文献18

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同被引文献16

  • 1杨志峰,王龙,杨生生,匡颖,陈欢,徐国江,蔡在龙,王铸钢,毛积芳.慢病毒载体介导IκB激酶-α(IKKα)基因RNA干扰转基因小鼠的制备[J].生物化学与生物物理进展,2007,34(2):215-221. 被引量:4
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  • 5Grigoryev DN, Liu M, Hassoun HT, et al. The local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol, 2008, 19: 547-558.
  • 6Goligorsky MS. Immune system in renal injtH'y and repair: burning the candle from both e, nds? Pharmaeol Res. 2008, 58:122-128.
  • 7Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int, 2004, 66: 480-485.
  • 8Nakamura A, Imaizumi A, Yanagawa Y, et al. beta (2)- Adrenoceptor activation attenuates eudotoxin- induced acute renal failure. J Am Soc Nephrol, 2004, 15: 316-325.
  • 9Lawrence T, Bebien M. IKKalpha in the regulation of inflammation and adaptive immunity. Biochem Soc Trans, 2007, 35 Pt 2: 270-272.
  • 10Li T, Morgan MJ, Choksi S, et al. MicroRNAs modulate the noncanonical transcription factor NF- kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation. Nat Immunol, 2010, 11: 799-805.

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