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目的:探索研究DNAJB6在部分肝移植肝再生的作用及分子机制。方法:采用DA大鼠作为供体,Lewis大鼠作为受体,构建部分肝移植肝再生模型。按照部分肝移植不同时间点分为6组(每组6对),分别为灌注前、劈裂肝完成灌注后、门静脉开放后、关腹前、术后第3、7天组。采用C57小鼠构建部分肝切除残余肝再生模型,根据肝切除不同时间点分为6组(每组6只),分别为对照组、1 d、2 d、3 d、4 d和5 d组。利用基因表达数据库的肝再生数据分析和肝再生动物标本找到肝再生的关键基因。通过转染干扰RNA构建DNAJB6低表达的人源肝细胞。通过蛋白印迹检测细胞增殖核抗原(PCNA)和细胞增殖实验研究DNAJB6与肝再生的关系。通过蛋白印迹检测核蛋白和经典细胞增殖信号通路节点蛋白研究DNAJB6调节部分肝移植肝再生的可能分子机制。结果:部分肝切除残余肝再生结果显示,DNAJ家族基因在再生肝基因芯片中差异表达,其中DNAJB6在再生肝基因芯片中低表达。与此同时,DNAJB6在部分肝移植和部分肝切的再生肝组织中低表达。DNAJB6沉默后,细胞PCNA表达水平升高且增殖速率加快。然而,细胞核提取没有检测到β-catenin胞核/质间改变,且Wnt4蛋白水平也未发生变化。虽然,Ras/MAPK下游的p38和JNK2活化水平没有发生变化,但ERK活化水平升高。结论:在再生肝组织中,肝细胞可能通过降低DNAJB6的表达水平抑制Ras/MEK/ERK信号通路以促进肝再生。“,”Objective:To explore the role and molecular mechanism of DNAJB6 in liver regeneration during partial liver transplantation(PLT).Methods:Dark agouti(DA, donor)and Lewis(recipient)rats were prepared for liver regeneration model of PLT.Rats were divided into before perfusion, after split liver perfusion, after portal vein opening, before abdominal closure and Day 3/7 after surgery groups(n=6 each)for timepoints of PLT.C57 mice were performed for residual liver regeneration model of partial hepatectomy and divided into control, Day 1/2/3/4/5 groups(n=6 each)for timepoints of hepatectomy.Gene Expression Omnibus liver regeneration data were utilized for locating DNAJB6 in liver regeneration.DNAJB6 low-expression human hepatocytes were constructed by DNAJB6-Si transfection.The relationship between DNAJB6 and liver regeneration was examined by Western blot detection of cell proliferation markers PCNA and CCK8 cell proliferation experiments.And the possible molecular mechanism of DNAJB6 regulating liver regeneration in PLT was studied by Western blot detection of nuclear protein and protein in cell proliferation signal pathway.Results:The result of residual liver regeneration of partial hepatectomy showed that DNAJ family genes were differentially expressed on regenerated liver gene chip and DNAJB6 was lowly expressed on regenerated liver gene chip.Meanwhile, DNAJB6 was lowly expressed in regenerated liver tissues of PLT and partial liver resection.After silencing DNAJB6 by transfecting DNAJB6-Si, the cellular expression level of PCNA and proliferation rate increased.However, nuclear extraction failed to detect the nuclear/plasma changes of β-catenin and the level of Wnt4 protein had no obvious change.Although the activation levels of p38 and JNK2 downstream of Ras/MAPK showed no change, there was a higher activation level of ERK.Conclusions:In regenerating liver tissue, hepatocytes may suppress the Ras/MEK/ERK signaling pathway by lowering the expression level of DNAJB6 to promote liver regeneration.