促红细胞生成素预处理对大鼠体外循环所致急性肾损伤的影响

Effects of erythropoietin preconditioning on acute renal injury induced by cardiopulmonary bypass in rats

目的观察促红细胞生成素(EPO)预处理对于大鼠体外循环(CPB)术后肾脏的保护作用。方法Sprague-Dawley(SD)大鼠均分为4组(n=10):假手术(Sham)组、模型(Control)组、低剂量EPO(Low EPO)和高剂量EPO(High EPO)组。于CPB术后24 h检测血清肌酐(Cr)水平,肾脏核因子-κB(NF-κB)p65、细胞间黏附分子-1(ICAM-1)及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6的表达水平,苏木精-伊红(HE)染色观察组织形态改变。结果Control组Cr[(141.99±6.96)μmol/L]高于Sham组[(37.98±1.22)μmol/L]和EPO干预组(均P<0.01),High EPO组[(67.52±5.63)μmol/L]低于Low EPO[(91.52±5.43)μmol/L,P<0.01)];相对于Control组TNF-α[(13.29±1.21) ng/mg]、IL-1β[(18.39±1.79) ng/mg]、IL-6[(10.95±1.03) ng/mg]、NF-κB p65(0.189±0.009)、ICAM-1(9.109±0.371),Low、High EPO干预后肾组织TNF-α[(9.41±0.72)、(7.85±0.67) ng/mg]、IL-1β[(12.35±1.43)、(10.18±2.01) ng/mg]、IL-6[(8.25±0.65)、(6.08±0.72) ng/mg]含量均下降(均P<0.01),NF-κB p65(0.165±0.003、0.151±0.005)、ICAM-1(6.847±0.310、5.013±0.462)表达亦显著下降。病理学显示EPO组的肾小管上皮细胞肿胀、胞质内空泡形成、间质出血等病理变化较模型组减轻,且High EPO效果明显。结论EPO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,对CPB术后大鼠肾脏损伤起保护作用,并呈剂量依赖性。

Objective To investigate the renal protective effect of erythropoietin (EPO) preconditioning on acute renal injury induced by cardiopulmonary bypass (CPB) in rats. Methods 40 male Sprague-Dawley rats were randomly divided into four groups: Sham, Control, Low and High EPO.24 h after the CPB, Blood samples were collected for assays of serum creatinine (Cr), meanwhile renal samples were obtained for the determination of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), nuclear factor-κB p65 (NF-κB p65), intercellular adhesion molecule-1 (ICAM-1), and for histologic examination. Results Compared with Control group (141.99±6.96)μmol/L, the levels of Cr decreased in Low EPO (91.52±5.43)μmol/L and High EPO group (67.52±5.63)μmol/L (P<0.01), levels of TNF-α[(9.41±0.72),(7.85±0.67) ng/mg], IL-1β[(12.35±1.43),(10.18±2.01) ng/mg], IL-6 [(8.25±0.65),(6.08±0.72) ng/mg], NF-κB p65 (0.165±0.003, 0.151±0.005), ICAM-1 (6.847±0.310, 5.013±0.462) in renal tissue of the Low and High EPO treated animals were significantly lower than those of the Control group (13.29±1.21) ng/mg,(18.39±1.79) ng/mg,(10.95±1.03) ng/mg,(0.189±0.009),(9.109±0.371)(all P<0.01). Histopathologic finding of the CPB group conflrmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. These changes were markedly reversed in EPO groups, High does EPO had a better renal protective effect (P<0.01). Conclusion EPO was effective on preventing CPB-induced renal injury probably through its downregulation of NF-κB p65. Furthermore, EPO attenuated these above changes dose dependently.