目的:初步探讨重组人肝再生增强因子(rhALR)保护及改善梗阻性黄疸大鼠肝细胞线粒体功能及肝功能的机制。方法:144只健康wistar大鼠随机分为SHAM组,BDO-RBF组,BDO—RBF-rhALR组,利用荧光定量PCR方法,对各组大鼠肝细胞总mtDNA、缺失型mtDNA进行相对定量检测。结果:胆道梗阻后,肝细胞线粒体总mtDNA拷贝数出现明显下降(P〈0.01),BDO—RBF—rhALR组总mtDNA拷贝数下降程度明显低于BDO—RBF组(P〈0.05);对于缺失型mtDNA占总mtDNA的百分比,在SHAM组,未检测出缺失型mtDNA,而在BDO—RBF组及BDO—RBF—rhALR组,均可见缺失型mtDNA,BDO—RBF组的缺失型mtDNA占总mtDNA的百分比明显高于BDO—RBF-rhALR组(P〈0.05);在胆道梗阻解除后,BDO—RBF—rhALR组的总mtDNA的拷贝数及缺失型mtDNA修复速度明显快于BDO—RBF组(P〈0.05)。结论:rhALR可通过保护及修复梗阻性黄疸大鼠肝细胞受损的mtDNA,达到保护及改善梗阻性黄疸大鼠肝细胞线粒体功能及肝功能的目的。
Objectives: To study the molecular mechanism of the beneficial effects of recombinant human augmentation factor of liver regeneration on mitochondrial function and liver function in obstructive jaundice rats. Methods: One hundred and forty four Wistar rats were randomly divided into three groups, namely SHAM, BDO-RBF, and BDO-RBF-rhALR. Quantify the changes of the whole mtDNA, deletion form mtDNA at selected time points in each group. Results: Compared to SHAM group, the copies of whole mtDNA reduced in obstructive jaundice rats (P〈0.01). Compared to BDO-RBF group, the copies of whole mtDNA reduced lighter in BDO-RBF-rhALR group (P〈0.05). The deletion form mtDNA was found in BDO-RBF and BDO-RBF groups, but not in SHAM group. There were more the percentage of deletion form mtDNA in whole mtDNA in BDO-RBF group than BDO-RBF-rhALR group (P〈0.05). The copies of whole mtDNA and the percentage of deletion form mtDNA in whole mtDNA in BDO-RBF-rhALR group recovered faster than BDO-RBF group after restoration of bile flow (P〈0.05). Conclusion: The recombinant human augmentation factor of liver regeneration protects mitochondrial and liver function because it can protect and repair damaged mtDNA in obstructive jaundice rats.