解整合素-金属蛋白酶9在小鼠酒精性肝纤维化过程中的表达  

Expression of ADAM9 in the process of alcoholic liver fibrosis in mice

作　　者：宋晓改 李三强[1] 文馨 郭威 李子昂 宋琢爽 魏鹏雪 王同园 杨欢 朱文枫 张兵兵 SONG Xiaogai;LI Sanqiang;WEN Xin;GUO Wei;LI Zi’ang;SONG Zhuoshuang;WEI Pengxue;WANG Tongyuan;YANG Huan;ZHU Wenfeng;ZHANG Bingbing(The Molecular Medicine Key Laboratory of Liver Injury and Repair,Medical College,the Second Affiliated Hospital of Henan University of Science and Technology,Henan University of Science and Technology,Luoyang 471000,China)

机构地区：[1]河南科技大学医学院肝脏损伤与修复分子医学重点实验室河南科技大学第二附属医院河南省肝病防治工程技术研究中心,河南洛阳471000

出　　处：《胃肠病学和肝病学杂志》2020年第7期810-813,817,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然基金资助项目(81201558);河南省科技创新杰出青年(184100510006);河南省高校科技创新团队项目(18IRTSTHN026)。

摘　　要：目的研究解整合素-金属蛋白酶9(ADAM9)在小鼠酒精性肝纤维化过程中的表达。方法将50只健康雄性C57BL/6J小鼠随机分为正常组10只,实验组40只。正常小鼠采用Lieber-DeCarli TP4030C对照液体饲料饲养小鼠8周,实验小鼠采用Lieber-DeCarli TP4030A酒精液体饲料喂养4周后联合5%四氯化碳橄榄油溶液2 ml/kg,腹腔注射,2次/周,总共8周诱导小鼠酒精性肝纤维化模型。分别于0、2、4、6、8周各取4只小鼠摘除眼球取血并分离血清,检测谷草转氨酶(AST)活性;颈椎脱臼处死小鼠并取肝,用免疫组化法测定0、2、4、6、8周小鼠肝组织中ADAM9蛋白的表达变化。结果小鼠经Lieber-DeCarli液体饲料喂养后0、2、4、6、8周AST活性分别为(110±14)U/L、(163±52)U/L、(200±26)U/L、(229±17)U/L、(509±111)U/L,从酶活性可以看出,酒精液体饲料喂养2周后,血清AST活性开始上升,随着喂养时间的增加,血清AST活性持续升高,8周达到最高值(P<0.01)。免疫组化结果显示,酒精液体饲料喂养2周后,ADAM9的蛋白表达量上升,随着喂养周数不断增加,ADAM9的蛋白表达量持续升高,8周达到最高值(P<0.01)。结论 ADAM9在小鼠酒精性肝纤维化过程中表达不断升高且变化显著,与肝纤维化的发展进程密切相关,可能起到促进肝纤维化的作用。Objective To investigate the expression of a disintegrin and metalloproteinase-9(ADAM-9) in alcoholic liver fibrosis in mice. Methods Fifty healthy male C57 BL/6 J mice were randomly divided into normal group(n=10) and experimental group(n=40). In normal mice, mice were fed with Lieber-DeCarli TP4030 C control liquid diet for 8 weeks. The mice were fed with Lieber-DeCarli TP4030 A alcohol liquid feed for 4 weeks and then combined with 5% carbon tetrachloride olive oil solution 2 ml/kg, intraperitoneal injection. Mice with alcoholic liver fibrosis were induced 2 times/week for a total of 8 weeks. Four mice were removed from the eyeballs at 0, 2, 4, 6 and 8 weeks to remove blood and separate the serum to detect the activity of aspartate aminotransferase(AST). The mice were sacrificed by cervical dislocation and the liver was taken and determined by immunohistochemistry. Expression of ADAM9 protein was detected in liver tissue of mice at 0, 2, 4, 6, and 8 weeks. Results The AST activities of mice at 0, 2, 4, 6 and 8 weeks after feeding with Lieber-DeCarli liquid diet were(110±14) U/L,(163±52) U/L,(200±26) U/L,(229±17) U/L,(509 ±111) U/L, it could be seen from the enzyme activity that serum AST activity began to increase after 2 weeks of feeding in liquid alcohol diet. As the feeding time increased, serum AST activity continued to increase, reaching the highest value in 8 weeks(P<0.01). The results of immunohistochemistry showed that the expression of ADAM9 protein was increased after 2 weeks of liquid alcohol diet feeding. As the number of feeding weeks increased, the expression of ADAM9 protein continued to increase, reaching the highest value in 8 weeks(P<0.01). Conclusion The expression of ADAM9 in the process of alcoholic liver fibrosis in mice is increasing and changing significantly, which is closely related to the development of liver fibrosis, which may promote liver fibrosis.

关 键 词：解整合素-金属蛋白酶9 酒精性肝纤维化 谷草转氨酶 Lieber-DeCarli液体饲料 

分 类 号：R575[医药卫生—消化系统]