人ALR205基因治疗大鼠急性肝损伤研究  

Study on treatmemt of acute hepatic injury in rats with human ALR205 gene

作　　者：陈罡 孔祥平 佟明华 游松 

机构地区：[1]解放军458医院全军传染病研究中心分子室,广东广州510602

出　　处：《中国热带医学》2009年第1期31-33,共3页China Tropical Medicine

基　　金：广东省自然科学基金项目(编号:04103063)

摘　　要：目的研究人肝再生增强因子(augmenter of liver regenerationALR)205基因对大鼠急性肝损伤的治疗作用。方法将200μg/kg重组质粒PCDNA3.1(+)-ALR205尾静脉注射给CCL4致急性肝损伤大鼠,检测血清AST、ALT水平,肝组织病理学变化、肝组织增殖细胞核抗原(Proliferating cell nuclear antigenPCNA)并对照ALR125基因治疗来观察ALR205基因对急性肝损伤的疗效。RT-PCR检测肝组织ALR205 mRNA表达情况。结果重组质粒用于急性肝损伤大鼠后,血清酶学检查结果表明外周血AST、ALT水平显著降低,肝组织病理损害情况大幅度减轻,治疗组肝PCNA指数均明显高于其它组且ALR205比ALR125在促肝细胞增殖方面有明显差异。结论ALR205基因体内表达产物通过促进肝细胞增殖,降低血清AST、ALT水平发挥抗急性肝损伤作用。Objective To construct the eukaryotic expression plasmid containing human ALR205 gene for exploring effect of gene therapy on acute hepatic injury in rats. Methods The ALR205 gene was amplified by RT-PCR method with total RNA extracted from the human hepatoma cell HepG2,then was cloned into the PCDNA3.1 （＋）.The recombinant plasmid of 200μg/kg was injected into the rats with acute hepatic injury by intravenous way after 4 hours of CCL4 administration.The level of AST and ALT in serum was determined by biochemical method, the hepatic-histopathological alteration was observed by HE staining,the PCNA was detected by immunohistochemistry staining and using PCDNA3.1 （＋）-ALR125 as positive control in order to observe protective effects of ALR205 gene on CCL4-intoxicated rats.RT-PCR could be used to prove the expression of ALR205 mRNA in the liver tissue. Results ALR205 gene was amplified successfully,which was consistent with the gene reported in GeneBank database.After the rats with acute hepatic injury were treated with the recombinant plasmid,the degree of liver histopathological injury and the concentration of AST and ALT in the serum were decreased significantly （P〈0.01）,the expression of PCNA was promoted （P〈0.01）,ALR205 and ALR125 have significant difference in proliferating hepatic cell（P〈0.05）. ALR205 were expressed only in the rats of therapy group. Conclusions PCDNA3.1（＋）- ALR205 may play an important role in relieving acute hepatic injury by promoting hepatic cell proliferation and reducing concentration of AST and ALT in CCL4-intoxicated rats.

关 键 词：肝再生增强因子 基因治疗 质粒 肝 大鼠 

分 类 号：Q78[生物学—分子生物学] R459.9[医药卫生—治疗学]