促红细胞生成素抑制大鼠体外循环术致急性肾损伤时NF-κB P65和ICAM-1表达

摘要

Objective Acute renal dysfunction is a common complication after cardiacsurgery with cardiopulmonary bypass ( CPB). This experiment is designed to investigate the expression of NF-KB P65 and ICAM-1 in renal tissue of rats undergoing cardiopulmonary bypass, and the protective mechanisms of erythropoietin ( EPO). Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: sham, CPB, EPO (3 000 U/kg EPO). Blood samples were collected at the beginning (TO) and the end of CPB(T1) , and 0. 5(T2) , 1 h(T3) , 2 h(T4) and 24 h(T5) after CPB for assays of serum creatinine. Renal samples were obtained 24 h after the operation for the determination of NF-KB P65, ICAM-1, and for histologic examination. Results Compared with those in the CPB group, the level of serum creatinine was lower in EPO group ( P < 0. 05 ). EPO had effective inhibitory effects on the expression of NF-KB P65 and ICAM-1 in renal tissues 24 h post-CPB (P <0. 05) , Histopathologic findings of the CPB group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. These changes were markedly reversed in EPO group. Conclusions The expression of NF-KB and ICAM-1 increase obviously in renal tissue of rats undergoing cardiopulmonary bypass, EPO can attenuate renal injury by inhibiting the activation and expression of NF-KB P65 and reduce the expression of ICAM-1.%目的 研究大鼠体外循环(CPB)术致急性肾损伤时肾脏核转录因子-κB(NF-κB) P65和内皮细胞表面黏附分子-1(ICAM-1)表达水平变化及促红细胞生成素(EPO)对其的抑制作用.方法 30只雄性SD大鼠随机分为3组(每组n=10):sham、CPB和EPO组,sham组建立CPB模型,不行体外转流,其余2组行体外转流,EPO组于转流前在预充液中加入3 000 U/kg的EPO.分别于肝素化后转流前(T0)和转流结束后(T1)、术后0.5(T2)、1(T3)、2(T4)和24 h(T5)检测血清肌酐水平,术后24 h取肾脏组织,HE染色观察组织形态,并分别采用免疫组化和West-ern blot法检测肾组织中NF-κB P65和ICAM-1表达.结果 术后CPB组各时间点与sham组比较血清肌酐水平均明显升高(P＜0.05),与CPB组相比,EPO组的肌酐水平明显下降(P＜0.05)；CPB组肾组织中NF-κB P65及1CAM-1表达水平均明显高于sham组(P＜0.05),EPO组NF-κB P65及ICAM-1表达水平均低于CPB组(P＜0.05)；病理学检查显示,EPO组的肾小管上皮细胞肿胀、胞质内空泡形成、间质出血明显减轻.结论 EPO可抑制大鼠体外循环后肾脏NF-κB P65及ICAM-1表达,从而减轻大鼠体外循环引起的肾脏损伤.