BNIP3在rhEPO促进大鼠部分肝切除后肝再生中的作用

BNIP3 involves in the process of erythropoietin promoting liver regeneration after partial hepatectomy in rat

目的由BNIP3介导的线粒体动态平衡在肝脏的脂肪代谢及糖代谢中起重要作用,而肝再生与线粒体代谢密切相关。有研究表明EPO可促进肝脏再生,但具体机制不明。本文研究重组人促红细胞生成素(rhEPO)对大鼠部分肝切除后肝功能及肝再生的影响,以及BNIP3和TNF-αmRNA在再生肝组织中的表达。方法36只Wistar大鼠随机分为rhEPO组和空白组,建立大鼠70%肝切除,肝切除后经门静脉注射3000IU/kg rhEPO,空白组注射等剂量生理盐水。术后1d、3d、5d各处死6只大鼠采集血清及肝脏标本,全自动生化分析仪测定血清谷丙转氨酶(ALT),免疫组织化学染色法检测Ki-67表达,ELISA法检测血清TNF-α、IL-6,荧光定量PCR检测肝组织BNIP3和TNF-αmRNA。结果肝切除术后1d rhEPO组的谷丙转氨酶(ALT)显著低于空白组(P<0.05)。肝切除术后1、5d rhEPO组Ki-67标记率显著高于空白组(P<0.05)。肝切除术后1d rhEPO组TNF-α显著高于空白组(P<0.05),肝切除术后1d 3d rhEPO组IL-6显著高于空白组。肝切除术后1d 3d rhEPO组BNIP3和TNF-αmRNA显著高于空白组(P<0.05)。结论门静脉注射rhEPO具有肝保护和明显的促肝再生作用,其机制可能与BNIP3和TNF-α有关。

Objective BNIP3 mediate mitochondrial dynamic equilibrium in liver fat metabolism and glucose metabolism. Mitochondrial metabolism plays an important role in liver regeneration. Some studies have shown that EPO may promote liver regeneration, but the exact mechanism is remained to be elucidate. We study the effect of recombinant human erythropoietin （rhEPO） on liver function and liver regeneration after partial bepatectomy in rats, as well as the expression of BNIP3 and TNF - cLmRNA in regenerating liver tissue. Methods 36 Wistar rats were randomly divided into the rhEPO group and blank group, and were submitted to 70% hepatectomy. The rhEPO group received 3000IU/kg of rhEPO tbrought portal vein injection and the blank control group received normal saline. Parameters of liver function and liver regeneration were assessed 1, 3, 5 days after 70% hepatectomy by means of automatic biochemical analyzer, immunohistochemicalstaining, ELISA assay and real -time PCR. Results 1 day significantly lower in rhEPO group than the blank group （P 〈 0. rhEPO group were significantly higher than the blank group （P rhEPO group were significantly higher than the blank group （P after hepatectomy alanine aminotransferase （ALT） were 05）. 1, 5 day after hepatectomy Ki -67 labeling rate in 〈 0.05 ）. lday after liver resection serum TNF - ct in 〈 0.05 ）, 1,3d ays after hepatectomy serum IL - 6 in rhEPO group were significantly higher than the blank group （P 〈 0.05 ）. 1,3days after liver resection, BNIP3 and TNF - α mRNA in rhEPO group were significantly higher than the blank group （P 〈 0. 05 ）. Conclusions Portal vein injection of rhEPO can protect liver function and promote liver regeneration, the mechanism may be related to BNIP3 and TNF - α.