中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (18): 3323-3328.doi: 10.3969/j.issn.1673-8225.2012.18.021

• 器官移植基础实验 basic experiments of organ transplantation • 上一篇    下一篇

远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1对肾脏缺血再灌注损伤的影响**★

李  炎1，吴家清1，申  升1，蒙善东1，周结学1，张  明2，刘  东1   

  1. 1南华大学医学院附属广东省第二人民医院器官移植中心，广东省广州市   510317；2上海交通大学医学院附属仁济医院肝脏外科，上海市  200127
  • 收稿日期:2011-12-11 修回日期:2012-02-09 出版日期:2012-04-29 发布日期:2012-04-29
  • 通讯作者: 刘东，主任医师，南华大学医学院附属广东省第二人民医院器官移植中心，广东省广州市 510317 antslydf@163.com
  • 作者简介:李炎★，男，1983年生，湖南省湘乡市人，汉族，2012年南华大学毕业，硕士，主要从事泌尿外科器官移植之肾脏缺血再灌注损伤保护机制研究。pioneer00.lee00@gmail.com
  • 基金资助:

    2010年广东省第一批产业技术研究与开发资金（2010B080701048），课题名称：缺氧诱导因子1a在肾缺血再灌注损伤中的作用；2011年度广东省自然科学基金（S2011010001333），课题名称：雷帕霉素在肾脏缺血再灌注损伤中的作用研究。

Effect of heat shock protein 27, erythropoietin and heme oxygenase-1 activated by remote ischemic preconditioning on kidney ischemia/reperfusion injury  

Li Yan1, Wu Jia-qing1, Shen Sheng1, Meng Shan-dong1, Zhou Jie-xue1, Zhang Ming2, Liu Dong1   

  1. 1Organ Transplant Center, Affiliated Guangdong Provincial N0.2 People’s Hospital, Medical School of University of South China, Guangzhou  510317, Guangdong Province, China; 2Deparment of Liver Surgery, Affiliated Renji Hospital, Medical College of Shanghai Jiao Tong University, Shanghai  200127, China
  • Received:2011-12-11 Revised:2012-02-09 Online:2012-04-29 Published:2012-04-29
  • Contact: Liu Dong, Chief physician, Organ Transplant Center, Affiliated Guangdong Provincial N0.2 People’s Hospital, Medical School of University of South China, Guangzhou 510317, Guangdong Province, China antslydf@163.com
  • About author:Li Yan★, Master, Organ Transplant Center, Affiliated Guangdong Provincial N0.2 People’s Hospital, Medical School of University of South China, Guangzhou 510317, Guangdong Province, China pioneer00.lee00@gmail.com
  • Supported by:

    The First Batch of Industrial Technology Research and Development Funds of Guangdong Province in 2010, No.2010B08070 1048*; Natural Science Foundation of Guangdong Province in 2011, No.S201101000 1333*

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328

被引次数

2

摘要：

背景：缺血再灌注损伤是临床导致急性肾衰竭等其他疾病的重要原因，其机制为多因素、多途径的复杂的病理过程。
目的：观察肾脏进行预处理后激活热休克蛋白、促红细胞生成素和血红素加氧酶1对肾脏缺血再灌注损伤的影响。
方法：雄性C57BL/6小鼠90只随机分成3组。缺血再灌注组为右肾切除，左肾缺血25 min再灌注24 h；预适应组为双侧肾脏缺血20 min再灌注8 d后再进行缺血再灌注。假手术组开腹游离肾蒂。
结果与结论：血清肌酐和尿素氮检测预适应组和假手术组明显低于缺血再灌注组(P < 0.01)；MPO染色发现缺血再灌注组大量中性粒细胞浸润(P < 0.01)；PAS染色发现预适应组肾组织病理情况轻于缺血再灌注组(P < 0.05)；TUNEL染色分析结果表明预适应组和假手术组细胞凋亡数明显少于缺血再灌注组(P < 0.01)；预适应组热休克蛋白27 mRNA表达明显高于缺血再灌注和假手术组(P < 0.05)，热休克蛋白27 mRNA于第8天时最强，促红细胞生成素、血红素加氧酶1 mRNA在24~    48 h达到峰值A，然后逐渐下降，第8天后达到峰值B，B>A，并且高于假手术组(P < 0.01)。提示远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1，能减少炎症因子浸润、促进肾小管细胞修复和抑制细胞凋亡从而参与肾脏内源性保护机制。

关键词: 缺血再灌注损伤, 肾脏缺血预适应, 小分子热休克蛋白, 促红细胞生成素, 血红素加氧酶1

Abstract:

BACKGROUND: Ischemia-reperfusion injury is the important reasons for acute renal failure and other disease, and the mechanism is mainly the multi-factor and multi-channel complex pathological process.
OBJECTIVE: To observe the influence of the heat shock protein 27 (HSP27), erythropoietin and heme oxygenase 1 activated by remote ischemic preconditioning in kidney ischemia/reperfusion injury.
METHODS: Ninety male C57BL/6 mice were randomly divided into three groups: ischemia/reperfusion group (n=30), preconditioning group (n=30), sham operation group (n=30). Mice in the ischemia/reperfusion group were removed the right kidney and the left kidney were subjected to ischemia for 25 minutes, and reperfusion for 24 hours; mice in the preconditioning group were subjected to bilateral renal ischemia for 20 minutes and were exposed to ischemia/reperfusion surgery on day 8 after reperfusion. Abdominal aortic blood was taken to test kidney function.
RESULTS AND CONCLUSION: Serum creatinine and blood urea nitrogen of preconditioning group and the sham operation group were significantly lower than that of the ischemia reperfusion group (P < 0.01); MPO staining found a large number of neutrophils infiltration in ischemia/reperfusion group (P < 0.01); PAS staining showed that the kidney histopathology of preconditioning group was better than that of ischemia reperfusion group (P < 0.05); TUNEL staining analysis displayed that the apoptosis cells in preconditioning and sham operation group were significantly less than that in the ischemia/reperfusion group   (P < 0.01); HSP27 mRNA expression in preconditioning group was significantly higher than that in the ischemia/reperfusion and sham operation group (P < 0.01), the peak of HSP27 mRNA expression was at 8 days, erythropoietin and heme oxygenase 1 mRNA were increased to A point during 24 and 48 hours, and then gradually decreased, but it was taken to another peak point B at 8 days and B was more higher than A, and the peak B in the preconditioning group was higher than that in the sham operation group (P < 0.01). Remote ischemic preconditioning activated HSP27, erythropoietin and heme oxygenase 1 mRNA expression can take part in reducing infiltration of inflammatory cytokines, promoting the repair of tubular cells and inhibiting the tubular cell apoptosis in order to protected the kidney ischemia/reperfusion injury.
 

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