不同价态饮水砷暴露对小鼠肝脏的损伤作用  

Hepatic damages in mice exposed to drinking water containing arsenic of different valence states

作　　者：李玲[1] 吴君[2] 蒋玲[1] 欧兵[2] 张韵[2] 李诚秀[1] 程明亮[2] 杨勤[3] 

机构地区：[1]贵阳医学院药理学教研室,贵阳550004 [2]贵阳医学院附属医院感染科,贵阳550004 [3]贵阳医学院病理生理学教研室,贵阳550004

出　　处：《第二军医大学学报》2008年第5期499-503,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30471592);中国肝炎防治基金会"王宝恩肝纤维化研究基金"(20070013)~~

摘　　要：目的:比较不同价态的饮水砷暴露对小鼠肝脏的损伤作用,探讨其可能的损伤机制。方法:60只雄性昆明种小鼠随机分为对照组(饮用蒸馏水)、300 mg/LiAs^(3+)暴露组(iAs^(3+)组)和300 mg/LiAs^(5+)暴露组(iAs^(5+)组),饮水砷暴露10个月后处死小鼠,检测各组小鼠肝功能、肝组织总砷含量,H—E染色及胶原特殊染色(Masson染色)观察各组小鼠肝组织病理学变化;实时荧光定PCR测定各组小鼠肝组织中TNF-α、IL-6、GSH-Px、MMP-8、ColⅠ和ColⅢmRNA的表达。结果:iAs^(3+)组小鼠肝组织中砷蓄积量高于iAs^(5+)组(P<0.05);iAs^(3+)组小鼠肝功能差于iAs^(5+)组(P<0.05);H—E染色及Masson染色结果表明iAs^(3+)组小鼠肝组织损伤及纤维化程度重于iAs^(5+)组。与对照组相比,iAs^(3+)、iAs^(5+)组小鼠肝组织TNF-α、IL-6、ColⅢmRNA表达明显升高(P<0.05),MMP-8 mRNA表达明显下降(P<0.05);与iAs^(5+)组相比,iAs^(3+)组小鼠肝组织TNF-α、IL-6、ColⅠmRNA表达升高(P<0.05)。结论:长期饮水砷暴露可能通过促进肝脏炎症介质及ECM分泌诱导慢性肝损伤、肝纤维化.肝损伤程度与砷的价态及蓄积量有关,且iAs^(3+)损伤作用强于iAs^(5+)。Objective：To compare the hepatic damaging effect in mice exposed to arsenic of different valence states （iAs^3＋ and iAs^5＋） and to probe into the related mechanisms. Methods： Sixty mice were divided into control group（distilled water）, sodium arsenite group（iAs^3＋ , 300 rag/L）and sodium arsenate group（iAs^5＋ 300 rag/L）at random. The mice were sacrificed 10 months after exposure in the 3 groups. The liver function and total arsenic content in the liver were examined in each group. H- E staining and Masson staining were employed to observe the pathologic changes of the livers. Real-time RT-PCR were used to examine the expression of TNF-α, IL-6 , GSH-Px, MMP-8, Col Ⅰ and Col Ⅲ mRNA. Results.. The accumulation of arsenic in iAs3＋ group was higher than that in the iAs^5＋ group; the liver function of animals in iAss＋ group was worse than that in the iAs^5＋ group （P〈0.05）. H-E and Masson staining showed that the hepatic injury and fibrosis in iAs3＋ group were severer than those in the iAs^5＋ group （P〈0.05）. The expression of TNF-α,IL-6,Col Ⅰ and Col Ⅲ mRNA was higher and the expression of GSH-Px,MMP-8 mRNA was lower in arsenic exposed mice compared with those in the normal mice （P〈0.05）. Compared with iAs5. ,animals in iAs^5＋ group had higher expression of TNF-α, IL-6, and Col Ⅰ mRNA （P%0. 05）. Conclusion： Long-term exposure to oral drinking with arsenic can result in hepatic injury and hepatic fibrosis by stimulating secretion of mediators of inflammation and ECM. And the effect of arsenic is related to the arsenic accumulation and the valence states of arsenic.

关 键 词：砷 肝 损伤 

分 类 号：R995[医药卫生—毒理学]