小鼠骨骼肌电转移hPDN1Q基因可以减轻CCl_4诱导的急性肝损伤  

Transgene Expression of Human Paraoxonase 1 Q (hPON1Q) Protects the Liver against CCl_4-induced Injury

作　　者：张驰[1] 陈博[1] 彭薇[1] 姜晓玲[1] 朱洁[1] 臧宇辉[1] 张峻峰[1] 秦浚川[1] 

机构地区：[1]南京大学生命科学院医药生物技术国家重点实验室,南京市210093

出　　处：《医学分子生物学杂志》2007年第3期195-199,共5页Journal of Medical Molecular Biology

基　　金：国家自然科学基金(No.30670858)~~

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,CCl_4)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CCl_4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CCl_4诱导的肝损伤具有显著的防护作用。Objective To investigate the transgene expression of human paraoxonase 1 Q （hPON1 Q） 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-induced liver injury. Results Serum arylesterase activities 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 assay 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 method for clinical treatment of liver injury.

关 键 词：Q型人对氧磷酶1 转基因表达 骨骼肌 电转移 肝损伤 

分 类 号：Q556[生物学—生物化学]