rhALR在大鼠部分肝移植术后肝再生中的作用及其机制研究  

ffect and mechanism of rhALR on liver regeneration after partial orthotopic liver transplantation in rats

作　　者：王震侠[1] 赵海平[1] 张瑞明[1] 董培德[1] 孟兴凯[1] 欧阳晓晖[1] 

机构地区：[1]内蒙古医学院附属医院普外科,内蒙古呼和浩特010050

出　　处：《肝胆胰外科杂志》2011年第4期332-335,共4页Journal of Hepatopancreatobiliary Surgery

基　　金：国家自然科学基金资助项目(30460131);内蒙古医学院附属医院重大科研课题(NYFYZD2008005)

摘　　要：目的探讨大鼠部分肝移植术后腹腔注射重组人肝再生增强因子(recombinant human augmenter ofliver regeneration,rhALR)促进肝移植术后肝细胞再生的作用及其机制。方法建立大鼠原位60%肝脏移植模型,部分肝移植术后腹腔注射rhALR 40μg/kg 2次/d(实验组,对照组注射等体积的注射用水);取术后第1、2、3、5、7天大鼠血清及肝组织,检测血清谷丙转氨酶(ALT),测定肝细胞PCNA LI的变化,RT-PCR检测肝组织IL-6 mRNA Cyclin-D1 mRNA的表达。结果实验组(A组)与对照组(B组)比较,术后第1、2天A组血清ALT显著低于B组。A组术后第1、2、3、5天的PCNA LI均明显高于B组同一时点的PCNA LI(P<0.05)。A组术后第2天的肝细胞AI明显低于B组同一时点的肝细胞AI(P<0.05);A组术后肝组织IL-6 mRNA的表达与B组在各观察时点间比较均无统计学差异(P>0.05);A组术后第1天肝组织Cyclin D1 mRNA的表达明显高于B组同时点的表达(P<0.05),其余观察时点无明显差异。结论大鼠部分肝移植术后应用rhALR可以明显促进肝细胞的再生,降低血清ALT,稳定肝细胞膜,保护肝细胞功能。rhALR促进大鼠部分肝移植术后的肝再生可能并不是通过上调启动阶段重要因子IL-6 mRNA的表达发挥作用,而是通过上调增殖阶段重要因子CyclinD1mRNA的表达发挥作用。Objective To investigate the role and mechanism of rhALR on liver regeneration after partial orthotopic liver transplantation in rats.Methods Rat model of 60% partial orthotopic liver transplantation was established.Rats were divided into two groups randomly,in group A,40 μg/kg rhALR was administered intraperitoneally twice a day after liver transplantation,and in group B,same vehicle of sterile water for injection was administrated as control.On the day of 1,2,3,5 and 7 respectively after operation in every group,the serum levels of ALT were detected,the expression of proliferating cell nuclear antigen labeling index（PCNA LI） was detected in liver sections,hepatocyte apoptotic index（AI） was evaluated with flow cytometry,and the expression of interleukin-6（IL-6） mRNA and Cyclin D1 mRNA in hepatic tissue were detected.Results Serum ALT level of group A was significantly lower than that of group B on the 1st,2nd post-operative day（POD）.PCNA LI in group A was significantly higher than that of group B on the 1st,2nd,3rd and 5th POD（P0.05）.The level of AI in group A was significantly lower than that of group B on the 2nd POD.There was no significantly difference in the expression of IL-6 mRNA between group A and B on every POD.The expression of Cyclin D1 mRNA of group A was significantly higher than that of group B on the 1th POD.Conclusion rhALR can promote the regeneration of hepatocyte after partial orthotopic liver transplantation in rats,decrease the level of serum ALT,and preserve hepatic function.The mechanism of rhALR in the promotion of hepatocyte regeneration can probably be to up-regulate the expression level of Cyclin D1mRNA in hepatic tissue but not IL-6 mRNA.

关 键 词：肝移植 肝再生增强因子 白细胞介素 细胞周期蛋白 大鼠 

分 类 号：R657.3[医药卫生—外科学]