Dual Effect of Erythropoietin on Liver Protection and Regeneration after Subtotal Hepatectomy in Rats
Dual Effect of Erythropoietin on Liver Protection and Regeneration after Subtotal Hepatectomy in Rats
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DOI：
10.1002/lt.22046
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发表时间：
2010-05-01
影响因子：
4.6
通讯作者：
Hochhauser, Edith
中科院分区：
文献类型：
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作者：
Greif, Franklin;Ben-Ari, Ziv;Hochhauser, Edith
目前为许多原发性或继发性肝脏肿瘤患者提供的唯一治疗选择是肝肿瘤切除术。本研究的目的是评估重组人促红细胞生成素（rhEPO）在大鼠肝大部切除术后肝脏保护和再生中的作用。接受 70% 肝切除术的大鼠在切除前 30 分钟腹腔注射生理盐水（对照）或 rhEPO (4 U/g)。通过测量国际标准化比值（INR）水平评估肝功能，通过血清丙氨酸转氨酶和天冬氨酸转氨酶水平评估肝损伤。通过肝内 caspase-3 活性和形态学标准评估肝细胞凋亡。通过再生肝脏/体重比、细胞增殖（Ki-67）和血管生成（血管性血友病因子）的免疫组织化学标记物以及磷酸化细胞外信号调节激酶信号传导，评估剩余肝脏的再生能力超过7天。肝次全切除术后第 2 天和第 4 天，用 rhEPO 治疗的动物的再生肝脏/体重比显着高于对照组（P < 0.005）。与对照组相比，用 rhEPO 预处理的动物在肝切除术后第 2 天和第 4 天的血清肝酶和 INA 水平显着降低（P < 0.005）。肝切除组之间的肝内肝 caspase-3 活性、caspase-3 免疫组织化学或末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记测定均无统计学显着差异。 rhEPO预处理组肝切除后第2天的有丝分裂指数、Ki-67和von Willebrand因子表达以及细胞外信号调节激酶活性均显着高于对照组（P < 0.05）。总之，rhEPO 治疗可能为大鼠肝大部切除术后立即的肝脏保护和再生提供独特的有益双功能策略。肝脏移植 16:631-638, 2010。(C) 2010 AASLD。
The only currently offered curative option for many patients with primary or secondary liver tumors is the resection of hepatic tumors. The aim of this study was to evaluate the role of recombinant human erythropoietin (rhEPO) in liver protection and regeneration after subtotal hepatectomy in rats. Rats undergoing 70% hepatectomy received an intraperitoneal injection of saline (control) or rhEPO (4 U/g) 30 minutes prior to resection. Liver function was assessed by the measurement of the international normalized ratio (INR) levels, and hepatic injury was assessed by serum alanine aminotransferase and aspartate aminotransferase levels. Hepatic apoptosis was assessed by intrahepatic caspase-3 activity and morphological criteria. The regeneration capacity of remnant livers was assessed over 7 days with the regenerated liver/body weight ratio, immunohistochemistry markers of cell proliferation (Ki-67) and angiogenesis (von Willebrand factor), and phosphorylated extracellular signal-regulated kinase signaling. Two and 4 days after subtotal hepatectomy, the regenerated liver/body weight ratio was significantly higher in animals treated with rhEPO versus the control group (P < 0.005). Serum liver enzymes and INA levels on days 2 and 4 post-hepatectomy were significantly lower in animals pretreated with rhEPO in comparison with the control group (P < 0.005). No statistically significant difference was noted in intrahepatic hepatic caspase-3 activity, immunohistochemistry for caspase-3, or a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay between the hepatectomized groups. In the rhEPO-pretreated group, the mitotic index, Ki-67 and von Willebrand factor expression, and extracellular signal-regulated kinase activity were significantly higher on day 2 post-hepatectomy (P < 0.05) in comparison with the control group. In conclusion, rhEPO treatment may offer a unique beneficial dual-function strategy for hepatic protection and regeneration immediately after subtotal hepatectomy in rats. Liver Transpl 16:631-638, 2010. (C) 2010 AASLD.