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目的:探讨应用腺病毒与乙型肝炎病毒嵌合载体表达胶原酶Ⅱ对肝硬化大鼠模型的治疗作用.方法:以硫代乙酰胺口服法16 wk诱导大鼠形成肝硬化模型,用腺病毒穿梭质粒与乙型肝炎病毒嵌合载体表达截断的胶原酶Ⅱ基因tMMP-8片断或全长MMP-8基因,分别构建了腺病毒Ad-CH-tMMP8、Ad-C-MMP8,并以表达红色荧光蛋白(red fluorescent protein,RFP2)的Ad-CH-RFP2作为对照,经尾静脉注射治疗已形成肝硬化模型的大鼠.结果:在Ad-CH-tMMP8、Ad-C-MMP8尾静脉注射肝硬化大鼠的体内转染研究中,转染4 wk相比于模型组,肝纤维化程度显著的减轻,肝细胞再生明显,同时伴有肝组织羟脯氨酸含量的下降(28.97μg/g±2.36μg/g vs 17.04μg/g±0.61μg/g,17.62μg/g±1.30μg/g,P<0.05),AdCH-RFP2对照组,纤维化程度同模型组类似.结论:用腺病毒与乙型肝炎病毒嵌合载体表达胶原酶Ⅱ能够有效地减轻大鼠肝纤维化程度.
Objective: To investigate the therapeutic effect of adenovirus and hepatitis B virus chimeric vector expressing collagenase Ⅱ on cirrhotic rat model.Methods: A rat model of cirrhosis was induced by thioacetamide for 16 weeks, The shuttle plasmid and Hepatitis B virus chimeric vector expressed the truncated collagenase Ⅱ gene tMMP-8 fragment or the full-length MMP-8 gene to construct the adenovirus Ad-CH-tMMP8 and Ad-C-MMP8 respectively, Ad-CH-RFP2 of red fluorescent protein (RFP2) was used as a control to induce the formation of liver cirrhosis model rats by tail vein injection.Results: In the tail vein of Ad-CH-tMMP8 and Ad-C-MMP8, In the in vivo transfection study of sclerosis rats, hepatic fibrosis was significantly relieved at 4 wk transfection compared with the model group, with significant hepatocyte regeneration accompanied by a decrease in hydroxyproline content in the liver (28.97 μg / g (P <0.05), and the degree of fibrosis in AdCH-RFP2 control group was similar to that in model group.Conclusion: Ad27-RFP2 cells were treated with adenovirus The expression of collagenase Ⅱ with the chimeric vector of hepatitis B virus can effectively reduce the degree of hepatic fibrosis in rats.