【摘要】 目的研究人Q型对氧磷酶1（human paraoxonase 1 Q,hPON1Q）转基因表达对小鼠四氯化碳（carbon tetrachloride,CCl₄）诱导急性肝损伤的缓解效果,为防治肝脏疾病寻找新的途径。方法小鼠骨骼肌直接注射含hPON1Q的真核表达质粒裸DNA并用电刺激介导表达,测量血清芳香酯酶的活性变化显示hPON1Q转基因表达效果,并使用血清谷丙转氨酶（ALT）、谷草转氨酶（AST）为指标及肝组织病理切片检测肝损伤的程度。结果hPON1Q转基因表达小鼠血清中芳香酯酶活性提高约50%,并可持续到16d以后。使用PON1裸DNA电刺激治疗组比对照组小鼠在用CCl₄诱导24h后血清芳香酯酶活性高60%,两种血清转氨酶指标及肝组织切片的病理学分析表明肝脏损伤程度有明显的减轻。结论电刺激介导的重组人PON1Q基因裸DNA在小鼠体内的表达对CCl₄诱导的肝损伤具有显著的防护作用。更多还原

【Abstract】 Objective To investigate the transgene expression of human paraoxonase 1 Q （hPON1Q） in mouse skeletal muscle and the protective effect against carbon tetrachloride （CCl₄） - induced liver damage.Methods Recombinant plasmid pcDNA3.0-hPON1Q was injected into mice skeletal muscle with electroporation （EP） in vitro and in vivo,and the arylesterase activities were measured to determine PON1 expression.Liver marker enzymes and hepatic histology were assayed to confirm the protective effect against CCl₄-indueed liver injury.Results Serum arylesterase activ- ities in PON1 transferred group increased by about 50 % as compared with the control groups,and the high level PON1 remained until the 16th day after the DNA injection.At the 10th day,CCl₄ was injected to induce liver damage.After 24 hours,serum arylesterase activities in PON1-transferred group were 60% higher than those in CCl₄ group.Serum ALT & AST activities and pathological as- say showed that liver injury in PON1-transferred group was significantly reduced.Conclusion Transgene expression of hPON1Q in mice skeletal muscle has an obvious protective effect against CCl₄-induced liver damage.This research may provide an effective,convenient and low-toxic meth- od for clinical treatment of liver injury.更多还原