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促红细胞生成素治疗对顺铂诱导的大鼠肾损伤进展的影响。

Effect of erythropoietin therapy on the progression of cisplatin induced renal injury in rats.

作者信息

Mohamed Hoda E, El-Swefy Sahar E, Mohamed Rasha H, Ghanim Amal M H

机构信息

Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Sharkia Gov., Zagazig 44519, Egypt.

出版信息

Exp Toxicol Pathol. 2013 Jan;65(1-2):197-203. doi: 10.1016/j.etp.2011.08.006. Epub 2011 Sep 15.

Abstract

Cisplatin is one of the most important chemotherapeutic agents useful in the treatment of a variety of solid tumors; however, it has several side effects such as nephrotoxicity. In the present study, the effect of rhEPO on acute kidney injury induced by i.p. injection of rats with 9.0 mg/kg cisplatin was studied. It was observed that EPO treated group showed a significantly lower rate in the extent and severity of the histological signs of kidney injury than untreated one. This is attributed to (i) a decrease in the elevated oxidative and nitrosative stress markers, (ii) reduction of the expression of VEGF, HO-1 and iNOS as well as (iii) improvement of Bcl2 immunoreaction in most tubular cells. Thus, EPO may be one of the futures therapeutic possibilities to overcome the side effects of anti-cancer drugs induced acute renal injury through various mechanisms including down regulation of vascular endothelial growth factor (VEGF), hemeoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) expressions in addition to stimulation of tubular cell regeneration.

摘要

顺铂是治疗多种实体瘤最重要的化疗药物之一;然而,它有多种副作用,如肾毒性。在本研究中,研究了重组人促红细胞生成素(rhEPO)对腹腔注射9.0mg/kg顺铂所致大鼠急性肾损伤的影响。观察到促红细胞生成素治疗组肾脏损伤组织学征象的程度和严重程度显著低于未治疗组。这归因于:(i)氧化应激和亚硝化应激标志物升高的降低;(ii)血管内皮生长因子(VEGF)、血红素加氧酶-1(HO-1)和诱导型一氧化氮合酶(iNOS)表达的降低;以及(iii)大多数肾小管细胞中Bcl2免疫反应的改善。因此,促红细胞生成素可能是未来通过多种机制克服抗癌药物诱导的急性肾损伤副作用的治疗选择之一,这些机制包括下调血管内皮生长因子(VEGF)、血红素加氧酶-1(HO-1)和诱导型一氧化氮合酶(iNOS)的表达以及刺激肾小管细胞再生。

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