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中文摘要：
目的 探讨人基质金属蛋白酶组织抑制物-1（tissue inhibitor of metalloproteinase-1,TIMP-1）对肾脏器官衰老过程血管生成的影响。方法 对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变化;Western免疫印迹检测TIMP-1、TIMP-2、基质金属蛋白酶（matrix metalloproteinase,MMP）-2、MMP-9、血管内皮细胞生长因子（VEGF）、Ⅲ型和Ⅳ型胶原蛋白质表达;明胶酶谱和反向酶谱分别检测明胶酶和TIMP-1的活性。结果 24月龄时与野生型小鼠相比,转基因小鼠肾小球和肾小管周围的微血管密度降低（P〈0.05）;TIMP-1、Ⅲ型和Ⅳ型胶原蛋白质表达增多（P〈0.05）,而MMP-2、MMP-9和VEGF的表达降低（P〈0.05）;明胶酶谱和反向酶谱结果显示,明胶酶的活性下调（P〈0.05）,而TIMP-1的活性则上调（P〈0.05）。结论 TIMP-1可能通过影响血管生成而促进肾脏器官衰老。 基金 国家重点基础研究发展规划（973项目,2007CB507403）;; 国家自然科学基金创新群体科学基金（30121005）
英文摘要：
Objective To explore the effect of tissue inhibitor of metalloproteinase （TIMP）-1 on renal angiogenesis with aging, Methods Changes of microvascular density （MVD） in kidneys in wild type mice and transgenic mice at the age of 3, 12, 24 months were observed by periodic acid-sliver methenamine （PASM） staining of para~n sections, The protein expressions of TIMP-1, TIMP-2, matrix metalloproteinase （MMP）-9, MMP-2, vascular endothelial growth factor （VEGF）, collagen m and 1V were detected by Western blot- ting, The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively, Results At the age of 24 months, MVD was lower, expressions of collagen m and 1V protein and TIMP-1 were higher, the expressions of MMP-2, -9 and VEGF were higher, the activities of gelatinases and TIMP-1 were downregulated and upregulated respectively （ all P 〈 0, 05 ）, Conclusions TIMP-1 could promote age-related renal insenecence through affecting angiogenesis.
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