中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (40): 7514-7519.doi: 10.3969/j.issn.2095-4344.2012.40.020

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

促红细胞生成素干预肾缺血再灌注损伤后肾小管间质的纤维化

陈 颖1,吴多江2,杨亦彬1,柯贵宝1,张富祥1,容 松3   

  1. 1遵义医学院附属医院肾内科,贵州省遵义市 563003
    2成都市郫县人民医院血透室,四川省成都市 611730
    3遵义医学院器官移植中心,贵州省遵义市 563003
  • 收稿日期:2012-05-14 修回日期:2012-07-20 出版日期:2012-09-30 发布日期:2012-09-30
  • 通讯作者: 容松,博士,教授,博士生导师,遵义医学院器官移植实验中心,贵州省遵义市 563003 songrong@hotmail.com
  • 作者简介:陈颖★,女,1986年生,湖北省宜昌市人,汉族,遵义医学院在读硕士,主要从事肾移植与临床免疫的研究。 yingzi86817@163.com

Effects of erythropoietin on renal tubulointerstitial fibrosis after renal ischemia-reperfusion injury in mice

Chen Ying1, Wu Duo-jiang2, Yang Yi-bin1, Ke Gui-bao1, Zhang Fu-xiang1, Rong Song3   

  1. 1Department of Nephrology, the Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China
    2Department of Hemodialysis, Pixian People’s Hospital, Chengdu 611730, Sichuan Province, China
    3Organ Transplantation Center, Zunyi Medical College, Zunyi 563003, Guizhou Province, China
  • Received:2012-05-14 Revised:2012-07-20 Online:2012-09-30 Published:2012-09-30
  • Contact: Rong Song, Doctor, Professor, Doctoral supervisor, Organ Transplantation Center, Zunyi Medical College, Zunyi 563003, Guizhou Province, China songrong@hotmail.com
  • About author:Chen Ying★, Studying for master’s degree, Department of Nephrology, the Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China yingzi86817@163.com

摘要:

背景:促红细胞生成素能减轻炎症反应、抗凋亡以及对缺血再灌注肾损伤有保护性作用。
目的:分析促红细胞生成素对肾缺血再灌注损伤后细胞凋亡和肾小管间质纤维化的关系。
方法:通过单侧肾缺血再灌注损伤构建患侧肾小管间质纤维化模型。实验小鼠随机分为4组:假手术组、缺血再灌注组、促红细胞生成素低剂量组和促红细胞生成素高剂量组。苏木精-伊红、Masson染色观察肾脏病理改变,免疫组织化学检测肾组织中Bcl-2和Bax蛋白表达水平,Western blot检测Caspase-3的表达。
结果与结论:与缺血再灌注组相比,两促红细胞生成素干预组肾小管和间质病变减轻。缺血再灌注组和两促红细胞生成素干预组肾脏Bcl-2和Bax表达均较假手术组明显上调,但缺血再灌注组更明显;缺血再灌注组Bcl-2/Bax比值较假手术组低,而两促红细胞生成素干预组Bcl-2/Bax比值却较缺血再灌注组高;两促红细胞生成素干预组Caspase-3表达高于假手术组而低于缺血再灌注组。结果表明,肾缺血再灌注损伤后期肾小管间质纤维化进程与细胞凋亡相关,Bcl-2/Bax及Caspase-3起了重要作用;低剂量促红细胞生成素也能减轻小鼠肾缺血再灌注损伤后期肾小管间质纤维化程度。

关键词: 促红细胞生成素, 肾缺血再灌注损伤, 肾小管间质纤维化, 细胞凋亡, Bcl-2, Bax, Caspase-3

Abstract:

BACKGROUND: Erythropoietin can relieve inflammation, anti-apoptosis and have a protective effect on renal ischemia-reperfusion induced injury.
OBJECTIYE: To investigate effect of erythropoietin on apoptosis and renal tubulointerstitial fibrosis renal ischemia-reperfusion-induced injury in mice.
METHODS: The tubulointerstitial fibrosis model was established by unilateral renal ischemia-reperfusion injury. All mice were divided into four groups: sham-operation group, ischemia-reperfusion group, low and high doses erythropoietin group. The renal pathological changes were observed by hematoxylin-eosin staining and Masson staining. Meanwhile, the expression of Bcl-2 and Bax protein in renal tissue was assessed by immunohistochemical method. The expression of Capase-3 was analyzed by Western Blot.
RESULTS AND CONCLUSION: Compared with ischemia-reperfusion group, the pathological changes of tubules and interstitium in low and high doses erythropoietin groups were significantly improved. Compared with the sham-operation group, the levels of Bcl-2 and Bax expression were remarkably increased in ischemia-reperfusion group and erythropoietin groups, and most significant in ischemia-reperfusion group; the ratio of Bcl-2/Bax in ischemia-reperfusion group was remarkably lower than that in the sham-operation group, and the ratio in the erythropoietin groups was higher than that in the sham-operation group. The Caspase-3 expression in erythropoietin groups was significantly higher than that in the ischemia-reperfusion group, but lower than that in the sham-operation group. It shows that the development of renal tubulointerstitial fibrosis after ischemia-reperfusion induced injury is related with the cell apoptosis, and the expression of Bcl-2/Bax and Caspase-3 plays an important role. Low dose erythropoietin can attenuate the renal tubulointerstitial fibrosis after renal ischemia-reperfusion injury.

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