促红细胞生成素减轻大鼠体外循环肾损伤的实验研究  

Erythropoietin reduces renal injury induced by cardiopulmonary bypass in rats

作　　者：王高明[1] 刘灿辉[1] 黄海嵘[1] 刘小龙[1] 申翼[1] 王常田[1] 李德闽[1] 景华[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)心胸外科,南京医学硕士研究生210002

出　　处：《医学研究生学报》2012年第5期466-470,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81172032)

摘　　要：目的急性肾损伤是心脏体外循环(cardiopulmonary bypass,CPB)术后常规并发症之一,文中研究促红细胞生成素(erythropoietin,EPO)对于大鼠体外循环肾损伤的保护作用并探讨相关机制。方法 30只雄性SD大鼠随机均分为3组(n=10):Sham组、CPB组、EPO组,Sham组建立CPB模型管道,不进行CPB,其余2组建立CPB,最大流量[≥100ml/(kg.min)]转流维持1 h,EPO组于转流前在预充液中加入3000 U的EPO。分别于肝素化后转流前(T0)和转流结束后(T1)、术后0.5h(T2)、术后1h(T3)、术后2h(T4)以及术后24h(T5)检测血清肌酐(creatinine,CR)、尿素氮(blood urea nitro-gen,BUN)水平,术后24 h取肾组织,检测组织肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素(inteleukin)-1β、IL-6及核因子-κB(nuclear factor-kappaB,NF-κB)P65、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达水平。并行HE染色观察组织形态改变。结果与CPB组相比,在T1至T5各时间点EPO组血清Cr、BUN水平明显下降(P<0.05),而在T0时3组无显著差异;肾组织中TNF-α、IL-1β、IL-6含量EPO组均明显低于CPB组(P<0.05);肾组织中NF-κBp65、ICAM-1 EPO组表达水平亦较CPB组显著下降(P<0.05);组织病理学检查显示EPO组的肾小管上皮细胞肿胀、细胞质内空泡形成、间质出血等病理变化明显减轻。结论 EPO可能通过抑制NF-κB p65的激活,进而下调ICAM-1、TNF-α、IL-1β、IL-6等炎性因子的表达,显著减轻CPB术后肾损伤。Objective Acute renal dysfunction is a frequent complication after cardiacsurgery with cardiopulmonary bypass （CPB）. This experiment was designed to investigate the effect of pretreatment with erythropoietin （EPO） on CPB-induced renal injury and its mechanism. Methods Thirty male SD rats were randomly divided into three groups of equal number： sham operation, CPB and EPO （CPB ＋ 3000 U/kg EPO）. The flow rate was maintained at 1〉 100 ml/kg/min for 1 h. Blood samples were collected at the be- ginning （T0） and the end of CPB （ T1 ）, and at 0.5 h （ T2）, 1 h （ T3 ）, 2 h （T4） and 24 h （ T5 ） after CPB for determination of the levels of Cr and BUN. Renal samples were obtained 24 h after the operation for the detection of TNF-a, IL-113, IL-6, NF-KB P65 and ICAM-1 as well as for histopathological examination. Results Compared with the CPB group, the levels of Cr and BUN were signifi- candy lower in the EPO group （ P 〈 0.05 ）, and so were the levels of TNF-a, IL-113 and IL-6 in the renal tissue （ P 〈 0.05 ）. EPO re- markably inhibited the expressions of NF-KB P65 and ICAM-1 in the renal tissue 24 h after CPB （ P 〈 0.05 ）. Histopathological findings confirmed renal impairment with cast formation and tubular necrosis in the tubular epithelia of the CPB group. These changes were markedly milder in the EPO group. Conclusion EPO can re- duce CPB-induced renal injury by suppressing the expression of in- flammatory cytokines. This anti-inflammatory effect of EPO is partly related to the inhibition of NF-kB P65 and ICAM-1.

关 键 词：促红细胞生成素 体外循环 肾损伤 炎性因子 

分 类 号：R692[医药卫生—泌尿科学]