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  

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

作　　者：陈颖[1] 吴多江[2] 杨亦彬[1] 柯贵宝[1] 张富祥[1] 容松[3] 

机构地区：[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

出　　处：《中国组织工程研究》2012年第40期7514-7519,共6页Chinese Journal of Tissue Engineering Research

基　　金：卫生部人类疾病比较医学重点实验室开放课题基金资助(ZDS200803)~~

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。BACKGROUND： Erythropoietin can relieve inflammation, anti-apoptosis and have a protective effect on rena ischemia-reperfusion induced injury. OBJECTIYE： To investigate effect of erythropoietin on apoptosis and renal tubulointerstitial fibrosis rena 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-reperrusion 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.

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 

分 类 号：R318[医药卫生—生物医学工程]