multiple doses of erythropoietin impair liver regeneration by increasing tnf-α, the bax to bcl-xl ratio and apoptotic cell death多剂量的促红细胞生成素损害肝脏再生通过增加tnf-α,伯灵顿bcl-xl比率和凋亡细胞死亡.pdfVIP

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multiple doses of erythropoietin impair liver regeneration by increasing tnf-α, the bax to bcl-xl ratio and apoptotic cell death多剂量的促红细胞生成素损害肝脏再生通过增加tnf-α,伯灵顿bcl-xl比率和凋亡细胞死亡.pdf

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multiple doses of erythropoietin impair liver regeneration by increasing tnf-α, the bax to bcl-xl ratio and apoptotic cell death多剂量的促红细胞生成素损害肝脏再生通过增加tnf-α,伯灵顿bcl-xl比率和凋亡细胞死亡

Multiple Doses of Erythropoietin Impair Liver Regeneration by Increasing TNF-a, the Bax to Bcl-xL Ratio and Apoptotic Cell Death 1. 1. ´ 1 1 2 Katja Klemm , Christian Eipel *, Daniel Cantre , Kerstin Abshagen , Michael D. Menger , Brigitte Vollmar1 1 Institute for Experimental Surgery, University of Rostock, Rostock, Germany, 2 Institute for Clinical Experimental Surgery, University of Saarland, Homburg, Germany Abstract Background: Liver resection and the use of small-for-size grafts are restricted by the necessity to provide a sufficient amount of functional liver mass. Only few promising strategies to maximize liver regeneration are available. Apart from its erythropoiesis-stimulating effect, erythropoietin (EPO) has meanwhile been recognized as mitogenic, tissue-protective, and anti-apoptotic pleiotropic cytokine. Thus, EPO may support regeneration of hepatic tissue. Methodology: Rats undergoing 68% hepatectomy received daily either high dose (5000 IU/kg bw iv) or low dose (500 IU/kg bw iv) recombinant human EPO or equal amounts of physiologic saline. Parameters of liver regeneration and hepatocellular apoptosis were assessed at 24 h, 48 h and 5 d after resection. In addition, red blood cell count, hematocrit and serum EPO levels as well as plasma concentrations of TNF-a and IL-6 were evaluated. Further, hepatic Bcl-xL and Bax protein expression were analyzed by Western blot. Principal Findings: Administration of EPO significantly reduced the expression of PCNA at 24 h followed by a significant decrease in restitution of liver mass at day 5 after partial hepatectomy. EPO increased TNF-a levels and shifted the Bcl-xL to Bax ratio towards the pro-apoptotic Bax resulting in significantly increased hepatoce