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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

20卷

期数:

2014年02期

页码:

89-092

栏目:

基础医学

出版日期:

2014-03-20

文章信息/Info

Title:

 Protective effects of z-VAD-FMK on renal ischemia-reperfusion injury in rat

文章编号:

1006-8147(2014)02-0089-04

作者:

于金宝¹; 王勇强²; 3; 崔尧丽²; 3; 王 兵²; 3; 王玉亮⁴

（1.天津医科大学一中心临床学院，天津 300192；2.天津市第一中心医院ICU科，天津 300192； 3.天津市急救医学研究所，天津 300192； 4.卫生部危重病急救医学重点实验室，天津 300384）

Author(s):

YU Jin-bao¹;  WANG Yong-qiang²; 3;  CUI Yao-li²; 3;  WANG Bing²; 3;  WNAG Yu-liang⁴

(1. Clinical Medicine College, First Center Hospital, Tianjin Medical University, Tianjin 300192, China; 2.Department of ICU,Tianjin First Center Hospital, Tianjin 300192, China; 3.Tianjin Institute of Emergency Medicine, Tianjin 300192, China; 4.Ministry Health Key Laboratory of Critical Care Medicine, Tianjin 300384, China)

关键词:

zVAD-fmk; 肾脏; 缺血再灌注损伤; 凋亡; caspase-3; caspase-8; 大鼠

Keywords:

zVAD-fmk;  kidney;  ischemia-reperfusion injury;  apoptosis;  caspase-3;  caspase-8;  rat

分类号:

R692

DOI:

-

文献标志码:

A

摘要:

 目的：探讨zVAD-fmk对大鼠肾缺血再灌注损伤的影响及其机制。方法：30只雄性SD大鼠随机分为3组：假手术组、对照组（DMSO组）、给药组（zVAD-fmk组），每组10只。对照组和给药组大鼠采用切除右肾，夹闭左侧肾动脉45 min后再恢复血流的方法制成肾缺血再灌注模型，于模型完成前15 min尾静脉给药；假手术组只切除右肾。模型成功后24 h收集大鼠血清和肾脏组织；测定血清肌酐（Scr）、尿素氮（BUN）；HE染色观察肾组织病理改变； TUNEL检测肾细胞凋亡； ELISA检测TNF-α、IL-10浓度；Western blot检测caspase-3和caspase-8表达。结果：与对照组相比，给药组Scr与BUN水平明显降低（P<0.01）；HE染色可见肾小管上皮细胞脱落、间质水肿、炎细胞浸润明显减少；肾小球和肾小管上皮细胞凋亡指数明显降低（P<0.01）； TNF-α、IL-10表达水平明显降低（P<0.01）；caspase-3和caspase-8表达明显降低（P<0.01）。结论::zVAD-fmk对大鼠肾缺血再灌注损伤有保护作用，其机制可能与抑制细胞凋亡，减轻炎症损伤有关。

Abstract:

Objective：To investigate the effects and the mechanism of zVAD-fmk in renal ischemia-reperfusion injury in rat. Methods： Thirty male adult SD rats were divided randomly into 3 groups: sham group, control (DMSO) group, drug (zVAD-fmk) treated group. The rats in control group and zVAD-fmk group were established at 45 min after the left renal artery occlusion on the basis of the right renal resection. Drugs were given through the tail vein 15 min before reperfusion, while the right kidney in rats was resected in the sham group but the left artery was not clamped. Kidneys and blood samples were obtained after reperfusion to determine serum creatinine (Scr) and blood urea nitrogen (BUN). Renal morphology dyed with HE was observed with microscope. TUNEL was used to detect the apoptosis of kidney cells. ELISA was applied to detect the levels of TNF-α and IL-10. Expressions of caspase-3 and caspase-8 protein were assessed by Western blot. Results：Compared with control group, plasma levels of Scr and BUN were significantly lower in the zVAD-fmk treated group(P<0.01); the slough of tubular epithelial cells, the edema of interstitial and the infiltration of inflammatory cells significantly decreased; the number of apoptotic glomerular cells also significantly decreased(P<0.01); the expressions of TNF-α, IL-10 were significantly lower (P<0.01); the expressions of caspase-3 and caspase-8 protein significantly decreased(P<0.01). Conclusion：zVAD-fmk can protect the renal ischemia-reperfusion injury in rat, which may be associated with the inhibition of apoptosis and inflammation.

参考文献/References:

 [1] Baitello A L, Marcatto G, Yagi R K. Risk factors for injury acute renal in patients with severe trauma and its effect on mortality[J]. J Bras Nefrol, 2013, 35 (2):127
[2] Hauser P, Oberbauer R. Tubular apoptosis in the pathophysiology of renal diseases[J]. Wien Klin Wochenschr, 2002, 114:671
[3] Saikumar P, Venkatachalam M A. Role of Apoptosis in Hypoxic/Ischemic Damage in the Kidney[J]. Semin Nephrol. 2003, 23(6):511
[4] Yang B, EI Nahas A M, Tisher M, et al. Inhibitors directed towards caspase-1 and -3 are less effective than pan caspase inhibition in preventing renal proximal tubular cell apoptosis[J]. Nephron Exp Nephrol, 2004, 96(2):e39
[5] Sheen-Chen S M, Ho H T, Chen W J, et al. Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat[J]. World J Gastroenterol, 2005, 11(15):2330
[6] Teng B T, Tam E W, Benzie I F, et al. Protective effect of caspase inhibition on compression-induced muscle damage[J]. J Physiol, 2011, 589(Pt 13):3349
[7] Nitescu N, Grimberq E, Ricksten S E, et al. Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early ischaemia-reperfusion injury in rats[J]. Clin Exp Pharmacol Physiol, 2006, 33(1/2):53
[8] Mersmann J, Zacharowski P A, Schmitz I, et al. Caspase inhibitor zVAD.fmk reduces infarct size after myocardial ischaemia and reperfusion in rats but not in mice[J]. Resuscitation, 2008 , 79(3):468
[9] Yoshida N, Iwata H, Yamada T, et al. Improvement of the survival rate after rat massive hepatectomy due to the reduction of apoptosis by caspase inhibitor[J]. J Gastroenterol Hepatol, 2007, 22(11):2015
[10] Esposito E, Cuzzocrea S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma[J]. Curr Med Chem, 2009, 16(24):3152
[11] Studer R K, Vo N, Sowa G, et al. Human nucleus pulposus cells react to IL-6：independent actions and amplification of response to IL-1 and TNF-α[J]. Spine, 2011, 36(8):593
[12] An S, Hishikawa Y, Liu J, et al. Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type II alveolar epithelial cells mediated by TNF-alpha and activation of Bid pathway[J]. Apoptosis, 2007, 12(11):1989
[13] Mosser D M, Zhang X. Interleukin-10: new perspectives on an old cytokine[J]. Immunol Rev, 2008, 226:205
[14] Kyrylkova K, Kyryachenko S, Leid M, et al. Detection of apoptosis by TUNEL assay[J]. Methods Mol Biol, 2012, 887:41
[15] Huppertz B, Frank H G, Kaufmann P. The apoptosis cascade morphological and immunohistochemical methods for its visualization[J]. Anat Embryol, 1999, 200(1):1
[16] Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways[J]. Cell, 2008, 133(4):693
[17] Yang B, Jain S, Ashra S Y. Apoptosis and caspase-3 in long-term renal ischemia/reperfusion injury in rats and divergent effects of immunosuppressants[J]. Transplantation, 2006, 81(10):1442

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备注/Memo

备注/Memo:

基金项目 国家临床重点专科建设经费及国家自然科学基金资助（81301624）
作者简介 于金宝（1987-），男，硕士在读，研究方向：急诊医学；通信作者：王勇强，E-mail：yongqiangwang1962@sina.com。

常用功能

更新日期/Last Update: 2014-03-30