肾上腺髓质素缺失对单侧输尿管结扎小鼠MMP-1/TIMP-1表达的影响  

Expression of MMP-1/TIMP-1 in adrenomedullin knockout mice with unilateral ureteral obstruction

作　　者：王香婷[1] 许庆友[2] 丁英钧[2] 王月华[2] 王筝[2] 谷艳丽[2] 张磊磊[2] 

机构地区：[1]河北医科大学中医学院中西诊断学教研室,河北石家庄050091 [2]河北医科大学中西医结合学院内科学教研室

出　　处：《中国老年学杂志》2010年第6期775-778,共4页Chinese Journal of Gerontology

基　　金：河北省科技厅资助项目(0520611034D-7)

摘　　要：目的探讨肾上腺髓质素在肾间质纤维化实验动物肾脏基质金属蛋白酶-1/基质金属蛋白酶抑制剂-1(MMP-1/TIMP-1)表达中的作用。方法结扎肾上腺髓质素基因敲除小鼠及野生小鼠单侧输尿管,制备肾间质纤维化实验动物模型并给予缬沙坦灌胃治疗,采用免疫组化、原位杂交、RT-PCR方法检测MMP-1及TIMP-1的表达。结果单侧输尿管结扎(UUO)小鼠肾脏MMP-1的表达减弱,而TIMP-1的表达显著上调,基因敲除小鼠较野生小鼠更为明显,采用缬沙坦治疗可部分抑制TIMP-1的表达。结论肾上腺髓质素可以通过纠正MMP-1/TIMP-1的失衡,对UUO介导的肾间质纤维化起到保护作用。Objective To investigate the effect of adrenomedullin on expression of MMP-1/TIMP-1 in adrenomedullin knockout （AMKO） and wild type （WT） mice with unilateral ureteral obstruction （UUO）.Methods Renal interstitial fibrosis model was made with UUO in AMKO and WT mice and treated with valsartan by oral.The expressions of matrix metalloproteinases-1 （MMP-1） and tissue inhibitor of metalloproteinases-1 （TIMP-1） were examined with immunohistochemistry,in site hybridization and RT-PCR.Results There was the unbalance of MMP-1/TIMP-1 because of down-regulated MMP-1 and up-regulated TIMP-1 in mice with UUO.Compared with those of WT mice,unbalance of MMP-1/TIMP-1 in AMKO mice were markedly and both of them partially were inhibited by valsartan.Conclusions Adrenomedullin has a role to against the renal interstitial fibrosis induced by UUO mice through its regulation on unbalance of MMP-1 and TIMP-1.

关 键 词：肾上腺髓质素 单侧输尿管结扎 基质金属蛋白酶-1 基质金属蛋白酶抑制剂-1 

分 类 号：R363.2[医药卫生—病理学] R693[医药卫生—基础医学]