新生大鼠窒息后肾组织Omi／HtrA2表达及Ucf-101干预效果

花兵; 董文斌; 李清平; 冯志强; 余鸿; 翟雪松; 雷小平

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中国当代儿科杂志 ›› 2010, Vol. 12 ›› Issue (08) : 658-661.

论著·实验研究

新生大鼠窒息后肾组织Omi／HtrA2表达及Ucf-101干预效果

花兵，董文斌，李清平，冯志强，余鸿，翟雪松，雷小平

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Effects of Ucf-101 on expression of Omi/HtrA2 in kidneys of postasphyxial neonatal rats

HUA Bing, DONG Wen-Bin, LI Qing-Ping, FENG Zhi-Qiang, YU Hong, ZHAI Xue-Song, LEI Xiao-Ping

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摘要

目的：探讨Omi／HtrA2在新生鼠窒息后肾组织的变化及Ucf-101的干预作用。方法：将72只7~10 d Wistar大鼠随机分为对照组、窒息组和Ucf-101组。窒息组和Ucf-101组大鼠制成常压窒息模型。在窒息30 min后复氧2、24、48 h时采用免疫组化法检测各组肾组织中Omi／HtrA2的表达。采用TUNEL法检测肾凋亡细胞的形态及数量变化。结果：窒息复氧后2 h Omi／HtrA2表达开始增强，于24 h达最高峰，随后有所下降。与窒息组相比，Ucf-101组各个时相点Omi／HtrA2的表达阳性率明显降低(P<0.01)。窒息复氧后2 h，肾组织开始出现肾小管上皮细胞凋亡，24 h凋亡细胞数达到高峰，而Ucf-101组各个时相点凋亡指数较窒息组均有明显减少。结论：新生大鼠窒息后肾组织Omi/HtrA2表达增强，参与肾损伤；Ucf-101可使Omi／HtrA2的表达下降，从而抑制肾小管上皮细胞凋亡。［中国当代儿科杂志，2010，12（8）：658-661］

Abstract

OBJECTIVE: To investigate the expression of serine protease Omi/HtrA2 in kidneys of postasphyxial neonatal rats, and to study the effects of Ucf-101 on apoptosis and the expression of Omi/HtrA2 in these rats. METHODS: Seventy-two neonatal Wistar rats of 7-10 days old were randomly divided into 3 groups: control, postasphyxial model, Ucf-101-treated postasphyxial．The postasphyxial model was established by normobaric asphyxia．Expression of Omi/HtrA2 was determined with streptavidin-peroxidase immunohistochemistry 2, 24 and 48 hrs after asphyxia. Terminal deoxynuleotidyl-mediated nick end labeling (TUNEL) was used to ascertain the apoptosis of renal cells. RESULTS: Compared with the control group, Omi／HtrA2 expression in renal cells began to increase 2 hrs after asphyxia and peaked at 24 hrs. The expression of Omi/HtrA2 in the Ucf-101-treated postasphyxial group was significantly lower than that in the postasphyxial model group (P<0.01). TUNEL-positive cells began to increase 2 hrs after asphyxia and peaked at 24 hrs in the postasphyxial model group when compared with the control group. The number of TUNEL-positive cells in the Ucf-101-treated postasphyxial group was significantly lower than that in the postasphyxial model group at all time points (P<0.01). CONCLUSIONS: The expression of Omi/HtrA2 in kidneys is increased in postasphyxial neonatal rats. The increased Omi/HtrA2 expression may play an important role in the development of postasphyxial renal injury. Treatment with Ucf-101 can reduce the expression of Omi/HtrA2 in kidneys of postasphyxial neonatal rats and thus reduce renal tububar epithelial cell apoptosis.［Chin J Contemp Pediatr, 2010, 12 (8):658-661］

导出引用

花兵, 董文斌, 李清平, 冯志强, 余鸿, 翟雪松, 雷小平. 新生大鼠窒息后肾组织Omi／HtrA2表达及Ucf-101干预效果[J]. 中国当代儿科杂志. 2010, 12(08): 658-661

HUA Bing, DONG Wen-Bin, LI Qing-Ping, FENG Zhi-Qiang, YU Hong, ZHAI Xue-Song, LEI Xiao-Ping. Effects of Ucf-101 on expression of Omi/HtrA2 in kidneys of postasphyxial neonatal rats[J]. Chinese Journal of Contemporary Pediatrics. 2010, 12(08): 658-661

中图分类号： R-33

参考文献

［1］董文斌，曹敏，王明勇，邓存良，陈枫，许开桂．新生儿窒息后血清诱导人肾小管细胞凋亡的作用［J］．实用儿科临床杂志，2005，20（12）：1207-1209.
［2］Wang CY, Lin YS, Su WC, Chen CL, Lin CF. Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis［J］. Mol Biol Cell, 2009, 20(19):4153-4161.
［3］董文斌，翟雪松，王兴勇，邓存良，赵春玲，张春来,等.新生鼠窒息后肾组织Na+、K＋-ATPase、TNF-α和NO的变化［J］．中华急诊医学杂志，2003，12（11）：737-738.
［4］张勇，董文斌，邓存良，王明勇，陈枫，许开桂. 窒息新生儿血清对肾小管上皮细胞内Omi／HtrA2表达的影响［J］．实用儿科临床杂志，2008，23（6）:436-437.
［5］Su D, Su Z, Wang J, Yang S, Ma J. UCF-101, a novel Omi/HtrA2 inhibitor, protects against cerebral ischemia/reperfusion injury in rats［J］. Anat Rec (Hoboken), 2009, 292(6):854-861.
［6］Althaus J, Siegelin MD, Dehghani F, Cilenti L, Zervos AS, Rami A. The serine protease Omi/HtrA2 is involved in XIAP cleavage and in neuronal cell death following focal cerebral ischemia/reperfusion［J］. Neurochem Int, 2007, 50(1):172-180.
［7］董文斌，杜逸亭，陈跃，航永伦，陈枫，邓存良．TNF-α含量的改变与肾小管细胞缺氧一复氧性损伤关系的研究［J］．细胞与分子免疫学杂志，2005，21(6)：690-692．
［8］Okazaki K, Kondo M, Kato M, Kakinuma R, Nishida A, Noda M, et al．Elevation of cytokine concentrations in asphyxiated neonates ［J］．Biol Neonate， 2006， 89(3)：183-189.
［9］Chang L，Kamata H，Solinas G，Luo JL, Maeda S, Venuprasad K, et al ．The E3 ubiquitin ligase itch couples JNK activation to TNF-α－induced cell death by inducing c-FLIP(L)turnover［J］．Cell， 2006， 124(3)：601-613.
［10］Belizario JE，Alves J，Occhiucci JS，Garay-Malpartida M, Sesso A. A mechanistic view of mitochondrial death decision pores［J］．Braz J Med Biol Res， 2007， 40(8)：1011-l024.
［11］Kin H，Wang NP，Halkos ME, Kerendi F, Guyton RA, Zhao ZQ. Neutrophil depletion reduces myocardial apoptosis and attenuates NF-κB activation /TNF-α release after ischemia and reperfusion ［J］．J Surg Res, 2006, 135（1）：170-178.
［12］Li Q, Hueckstaedt LK, Ren J.UCF101 Ameliorates streptozotocin-induced cardiomyocyte contractile dysfunction in vitro: role of AMP-activated protein kinase［J］. Exp Physiol, 2009, 94(9):984-994.
［13］Liu HR, Gao E, Hu A, Tao L, Qu Y, Most P, et al. Role of Omi/HtrA2 in apoptotic cell death after myocardial ischemia and reperfusion［J］. Circulation, 2005, 111(1):90-96.
［14］Bhuiyan MS, Fukunaga K. Activation of HtrA2, a mitochondrial serine protease mediates apoptosis: current knowledge on HtrA2 mediated myocardial ischemia/reperfusion injury［J］. Cardiovasc Ther, 2008, 26(3):224-232.