摘 要:
目的：建立二甲基亚硝胺（Dimethylnitrosamine,DMN）诱导的小鼠肝损伤模型,探讨其发生机理。方法：分别以DMN30mg·kg^-1、20mg·kg^-1、15mg·kg^-1腹腔注射小鼠,筛选出最佳的DMN剂量,以DMN15mg·kg^-1腹腔注射小鼠,对照组小鼠腹腔注射生理盐水,观察各时间点小鼠肝组织病理学变化和血清ALT、AST、白蛋白指标,定量PCR法检测肝组织TNF-α、Fas、MMP-2mRNA、MMP-9mRNA的动态表达。结果：腹腔注射DMN15mg·kg^-1可使大部分小鼠存活到120小时以上,且伴有显著的肝损害。DMN造模后的各时间点TNF-αmRNA表达明显升高,MMP-2mRNA表达先升高后降低,而MMP-9mRNA表达则持续升高。结论：DMN诱导的小鼠肝损伤模型,其机理与TNF-α表达升高密切相关。该模型肝损害后MMP显著升高,破坏了正常的细胞外基质,促进了肝组织炎症的扩散,这可能是肝损害的发生机理之一。[著者文摘]
Establishment of mouse of liver injury induced by dimethylnitrosamine and mechanism of the model
ZHANG LING,JIANG YUAN,HE JIN-YANG,et al.
1.Department of Internal Medicine ,Affiliated Shenzhen Shajing Hospital of Guangzhou Medical College,（Shenzhen Guangdong,518104）
Abstract:
Objective：To establish mouse model of liver injury induced by dimethylnitrosamine and investigate the mechanism of the model.Methods：Mice were treated with DMN at dose of 30 mg·kg^-1,20mg·kg^-1,15mg·kg^-1,i.p,respectively,and optimal dose was choosed.Mice were treated with DMN at dose of 15mg·kg^-1,i.p,and the control group received an equivalent amount of saline.Histopathology of liver tissues and serum of ALT,AST and albumin in different times were observed.Quantitative polymerase chain reaction （PCR） was applied for the detection of TNF-α,Fas,MMP-2,MMP-9 mRNA expression.Results：Most mice survived until 120 hours and liver injury was very obvious after treated with DMN at dose of 15mg ·kg^-1,i.p.In different times after DMN treatment,TNF-α mRNA expression increased distinctnively and MMP-2 mRNA expression elevated first and then decreased,while MMP-9 mRNA expression increased continuously.Conclusion：Mouse model of liver injury induced by dimethylnitrosamine is successfully made.The mechanism of the model related to the rise of TNF-α mRNA expression.Matrix metalloproteinases is increased after liver injury,which destroyed extracellular matrix of well-balanced liver,and promoted proliferation of liver tissues inflammation,which may be the common mechanism of liver injuury.[著者文摘]
Key words:
dimethylnitrosamine; liver injury; histopathology; tumor necrosis factor-alpha
全文可向本站在线客服索取
www.uarlab.com
