基质金属蛋白抑制因子-1 mRNA在饮水砷暴露肝损伤小鼠肝组织中的表达  

Expression of tissue intbitor of metalloproteinase-1 mRNA in hepatic tissue in mice exposed to drinking arsenic

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

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

出　　处：《中国地方病学杂志》2007年第6期603-606,共4页Chinese Jouranl of Endemiology

基　　金：国家自然科学基金(30471592);科技部国际科技合作与交流专项经费项目(2005DFA30640;A类)

摘　　要：目的探讨基质金属蛋白酶抑制因子-1(TIMP-1)mRNA在饮水砷暴露肝损伤小鼠肝组织中的表达及意义。方法50只雄性小鼠被随机分成对照组、亚砷酸钠组(iAs^(3+)组,300 mg/L)、砷酸钠组(iAs^(5+)组,300 mg/L)。10个月后处死小鼠,肝功能检查血清丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、球蛋白(GLB);部分肝组织进行HE染色;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及纯度,实时荧光定量PCR法测定肝组织中TIMP-1 mRNA的表达,以18S基因作为质控。结果ALT在对照组(36.67±3.51)、iAs^(3+)组(61.46±13.85)和iAs^(5+)组(43.31±4.21)组间比较差异有统计学意义(F=6.559,P<0.05);iAs^(3+)组与对照组比较差异有统计学意义(P<0.05),iAs^(5+)组与对照组、iAs^(3+)组比较差异无统计学意义(P>0.05);AST在对照组(135.00±20.42)、iAs^(3+)组(510.86±59.01)和iAs^(5+)组(258.93±22.40)组间比较差异有统计学意义(F=83.327,P<0.05);GLB在对照组(20.86±0.61)、iAs^(3+)组(26.94±3.73)和iAs^(5+)组(24.59±5.27)组间比较差异无统计学意义(F=2.800,P>0.05)。肝组织病理检查显示,肝组织中有明显的肝细胞坏死和再生,TIMP-1 mRNA表达组间比较差异有统计学意义(F=17.337,P<0.05)。结论TIMP-1基因在水砷暴露肝损伤小鼠肝组织损伤、肝纤维化形成过程中可能起重要作用。Objective To study the expression and its significance of tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA in hepatic tissue in mice drinking water containing arsenic. Methods 50 mice were divided into control group, sodium arsenite group （iAs^3＋ group, 300 mg/L） and sodium arsenate group （iAs^3＋group, 300 mg/L） at random. The mice were sacrificed 10 months afterwards, serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, globulin （GLB） were detected. Some liver tissue were HE stained and extracted of the total RNA by trizol-phenol-chloroform method, its purity was further detected with spectruphotometry and the expression of TIMP-1 mRNA was determined with real time fluorescence quantitative PCR. Finally, the result was controlled with 18S gene. Results Serum ALT among control group （36.67 ± 3.51 ）, iAs^3＋ group （61.46 ± 13.85） and iAs^3＋ group （43.31 ± 4.21） had statistical significance （F = 6.559,P 〈 0.05）, expecially between the control group and iAs^3＋ group （P 〈 0.05）, but there no significance between either iAs^3＋ group and control group or iAs^3＋ group and iAs^3＋ group（P 〉 0.05） ; Serum AST had statistical significance among control group（ 135.00 ± 20.42）, iAs^3＋ group（510.86 ± 59.01） and iAs^3＋. group （258.93 ± 22.40）（F = 83.327,P 〈 0.05）; Serum GLB had no statistical significance among control group （20.86 ± 0.61）, iAs^3＋ group （26.94 ± 3.73） and iAs^3＋ group （24.59 ± 5.27）（F = 2.800,P 〉 0.05）. Pathologic examination identified notable liver cell necrosis and regeneration. The expressions of TIMP-1 mRNA were statistically different among the three groups （F = 17.337,P 〈 0.05）. Conclusions The TIMP-1 gene may play a significant role in the process of hepatic injury and hepatic fibrosis due to drinking arsenic water in mice.

关 键 词：饮水 砷中毒 基质金属蛋白酶抑制因子-1 肝纤维化 肝损伤 

分 类 号：R599[医药卫生—内科学] R575[医药卫生—临床医学]