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目的探讨亚砷酸钠对大耳兔肝脏基质金属蛋白酶抑制因子-1(TIMP-1)mRNA和蛋白表达的影响。方法将30只健康成年清洁级雄性新西兰大耳兔随机分为5组,每组6只,分别为对照(自来水)组及0.15、0.30、0.75、1.5 mg/ml亚砷酸钠染毒组。采用自由饮用方式进行染毒,连续染毒12周。染毒结束后,分别采用酶联免疫吸附(ELISA)法和实时荧光定量PCR(RT-PCR)法检测大耳兔肝组织中TIMP-1蛋白和mRNA的表达水平。结果与对照组相比,各剂量亚砷酸钠染毒组大耳兔肝组织中TIMP-1蛋白和0.30、0.75、1.5 mg/ml亚砷酸钠染毒组大耳兔肝组织中TIMP-1 mRNA的表达水平均较高,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒剂量的升高,大耳兔肝组织中TIMP-1蛋白及mRNA表达水平均呈上升趋势。结论基质金属蛋白酶抑制因子-1(TIMP-1)表达的增高可能是亚砷酸钠肝毒性的易感因素。
Objective To investigate the effect of sodium arsenite on mRNA and protein expression of matrix metalloproteinase-1 (TIMP-1) in the liver of a large eared rabbit. Methods Thirty healthy adult male New Zealand white rabbits were randomly divided into 5 groups (6 rats in each group), which were control (water) group and 0.15, 0.30, 0.75, 1.5 mg / ml sodium arsenite exposure group respectively. Using free drinking method for exposure, continuous exposure for 12 weeks. After the exposure, ELISA was used to detect the expression of TIMP-1 protein and mRNA in the liver tissue of rabbits with real-time quantitative PCR (RT-PCR). Results Compared with the control group, TIMP-1 protein in liver tissue of auricles of each dose of arsenite treatment group and liver tissue of auricles of 0.30, 0.75, 1.5 mg / 1 mRNA expression levels were significantly higher (P <0.05). With the increase of the dose of sodium arsenite, the expression of TIMP-1 protein and mRNA in the liver tissue of large-eared rabbits Upward trend. Conclusion The increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a susceptible factor to the hepatotoxicity of sodium arsenite.