重组人红细胞生成素对脓毒症大鼠肾脏的保护作用

目的 探讨重组人红细胞生成素(rHuEPO)对盲肠结扎穿孔术(CLP)所致大鼠脓毒症急性肾损伤(AKI)的保护作用.方法 260只雄性SD大鼠随机分为正常对照组、假CLP组(假手术组)、CLP组(脓毒症组)和rHuEPO大、中、小剂量组.采用CLP复制脓毒症模型,rHuEPO大、中、小剂量组造模后即刻分别静脉推注rHuEPO 5000 U/kg、1000 U/kg、500 U/kg.假CLP组、CLP组、rHuEPO大、中、小剂量组按注药后2h、6h、12 h、24 h、36 h时点分成5个亚组,分别在各时点按随机原则处死大鼠.采用ELISA法测定血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、肾损伤分子1(KIM-1)、诱导型一氧化氮合酶(iNOS)的水平；免疫组化法检测大鼠肾组织NF-κB蛋白表达；光镜和透射电镜观察肾组织形态学变化.结果 与CLP组相比,rHuEPO大剂量组大鼠各时间点血清Scr、BUN、TNF-α、IL-6、KIM-1、iNOS的含量及肾组织NF-κB蛋白表达水平均显著降低,差异有统计学意义(P＜0.05)；肾脏病理改变好转.rHuEPO中、小剂量组肾脏病理改变未见好转.结论 rHuEPO能够降低脓毒症大鼠血清TNF-α、IL-6、iNOS、KIM-1水平进而调节炎性反应及肾功能,对脓毒症所致AKI具有一定的保护作用.

Recombinant human erythropoietin as a novel agent with pleiotropic effects against sepsis-induced acute kidney injury

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)?induced acute kidney injury (AKI). Methods A total of 260 healthy male Sprague?Dawley rats (250?300 g) were randomly divided into 6 groups: normal control group, sham group, CLP model group, the large dose rHuEPO (5000 U/kg) group, the middle dose rHuEPO (1000 U/kg) group, and the small dose rHuEPO (500 U/kg) group. The rat models of sepsis were established by CLP. In treatment groups, rats were treated with rHuEPO through caudalis injection after CLP surgery. Each group was divided into 2?, 6?, 12?, 24?, 36?hour subgroups with 10 rats. Rats were sacrificed and the tissue samples including kidney and blood samples were collected. The kidney function, plasma cytokines [interleukin 6 (IL?6) and tumor necrosis factor alpha (TNF?α)], kidney injury moleclue 1 (KIM?1) and inducible nitric oxide synthase (iNOS) were measured. Cytokines were determined by ELISA method. The expression of nuclear factor?kappaB (NF?κB) protein in kidneys were detected by immnunohistochemistry method. Pathological changes of kidney tissues were observed by light and transmission electron microscopy for cytokine content and apoptosis. Results Compared with CLP model group, renal function, the levels of TNF?α, IL?6, KIM?1 and iNOS in serum, the expression of NF?κB, significantly decresed in large dose rHuEPO group (all P＜0.05). rHuEPO also lessened the histological changes in large dose group. rHuEPO did not lessen the histological changes in others. Conclusion rHuEPO can inhibit the levels of TNF?α, IL?6 and iNOS in serum, thus modify the inflammatory response and provide protective effects against acute kidney injury induced by sepsis.