【摘要】 目的探讨促肝纤维化因子基质金属蛋白酶-8(MMP-8)、基质金属蛋白酶抑制因子-2(TIMP-2)和Ⅰ、Ⅲ型胶原(Col-Ⅰ、Col-Ⅲ)在水砷暴露小鼠肝组织中的表达及其意义。方法50只雄性小鼠被随机分成对照组、亚砷酸钠组和砷酸钠组。亚砷酸钠组和砷酸钠组给予普通饲料和砷溶液。10个月后处死小鼠,血清进行肝功能检测;苏木素-伊红(HE)染色部分肝组织;Trizol-酚-氯仿一步法提取小鼠肝组织总RNA,紫外分光光度法测定总RNA浓度及纯度,实时荧光定量PCR法测肝组织中MMP-8、MMP-2、Col-Ⅰ、Col-ⅢmRNA的表达,以18S基因作为质控。结果亚砷酸钠组、砷酸钠组血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、球蛋白(GLB)值均高于对照组;肝组织病理检查显示有明显的肝细胞坏死、再生和少许纤维化;与对照组比较,亚砷酸钠组肝组织Col-Ⅰ、Col-ⅢmRNA表达的差异均有统计学意义(tCol-Ⅰ=5.49,tCol-Ⅲ=8.64,P<0.05);MMP-8 mRNA降低差异有统计学意义(t=7.35,P<0.05);砷酸钠组TIMP-2、Col-Ⅰ、Col-ⅢmRNA差异均有统计学意义(tTIMP-2=6.72,tCol-Ⅰ=13.59,tCol-Ⅲ=9.68,P<0.05);MMP-8 mRNA降低差异有统计学意义(t=6.28,P<0.05)。结论长期饮水砷暴露,可导致慢性肝损伤、肝纤维化;TIMP-2、MMP-8基因在砷致小鼠纤维化发生中起重要作用。更多还原

【Abstract】 Objective To study the expression and its significance of MMP-8\,Col-Ⅰ、Col-Ⅲ mRNA in hepatic tissue in oral arsenic solution exposed mice.Methods 50 mice werer divided into control group,sodium arsenite group and sodium arsenate group at random.Sodium arsenite group and sodium arsenate group were made by 300 mg/L per day of sodium arsenite and sodium arsenate respectively.The mice were sacrificed after 10 months for liver function and pathologic examination.The expression of MMp-8,TIMP-2,Col-Ⅰ、Col-Ⅲ mRNA were detected with real time flourescence quantitative PCR.The result was controlled with 18s.Results Serum ALT、AST、GLB of arsenic exposed mice were higher than that of nomal mice.Pathologic examination showed that there were notable liver cell necrosis,regeneration and a little fibrosis.The expression of Col-Ⅰ、Col-Ⅲ mRNA in sodium arsenite group were higher than the nomal’s(tCol-Ⅰ=5.49,tCol-3=8.64,P<0.05);MMP-8 mRNA in sodium arsenite group were lower than the normal’s(t=7.35,P<0.05);The expression of TIMP-2,Col-Ⅰ、Col-Ⅲ mRNA in sodium arsenate group were higher than the normal’s(tTIMP-2=6.72,tCol-Ⅰ=5.49,tCol-3=8.64,P<0.05);MMP-8 mRNA in sodium arsenate group were lower than the normal’s(t=6.28,P<0.05).Conclusion Exposed to arsenic solution orally,could result in hepatic injury and hepatic fibrosis in mice and the TIMP-2,MMP-8 gene play significant effect in process of hepatic fibrosis.更多还原