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Expression of tissue inhibitor of matrix metalloproteinase-1 in aging of transgenic mouse liver

ISSN号：0366-6999
期刊名称：《中华医学杂志：英文版》
时间：0
分类：R575[医药卫生—消化系统;医药卫生—临床医学;医药卫生—内科学]
作者机构：[1]Department of Nephrology, General Hospital of PLA, Beijing100853, China, [2]Department of Nephrology, Beijing Military Command GeneralHospital, Beijing 100700, China
相关基金：This study was supported by grants from the Major State Basic Research Development Program of China （973 Program, Creative Research Group Fund of the National Science Foundation of China （No. 30121005）, and Postdoctor Foundation of China （No. 2004035048）.

作者： ZHANG Yu-mei[1,2], CHEN Xiang-mei[1], WU Di[1], ZHANG Xue-guang[1], LU Yang[1], SHI Suo-zhu[1], YIN Zhong[1]

关键词：组织抑制剂, 肝脏, 小鼠, 动物实验, 氧化作用, aging, tissue inhbitor of matrix metallporoteinase-1, transgenic mice, fiver, oxidative

中文摘要：

矩阵 metalloproteinase-1 (TIMP-1 ) 的背景织物禁止者与许多机关的老化有关，但是很少数据在在肝老化的 TIMP-1 的变化上是可得到的。这研究的 Thepurpose 是在正常、转基因的鼠标的肝在自然老化的进程调查 TIMP-1， matrixmetalloproteinase-2 (MMP-2 ) 和 MMP-9 的表达式和角色，并且在氧化水平和转基因的小鼠标的肝的抗氧化的能力上检测 TIMP-1 的效果。方法正常、转基因的老鼠根据他们的年龄被划分成 3groups：3-month-old 组(n=5 ) ， 12-month-old 组(n=5 ) 和 24-month-oldgroup (n=5 ) 。肝的组织病理学说的变化被观察在以后他和染色的马森。TIMP-1， MMP-2 和 MMP-9 的 Themessenger RNA (mRNA ) 层次被半量的 reversetranscriptional 聚合酶链反应决定；蛋白质表示被西方的污点在各种各样的年龄的正常、转基因的老鼠的肝测量。在超级氧化物 dismutase (草皮) 的层次的变化，单音的胺 oxidase (毛) ， malondialdehyde (MDA ) 象一样氧化并且 anti-oxidativeability 被测量。组织学地结果，当他们月的年龄增加了，更多的丰满的退化和骨胶原免职正常老鼠比在那些在转基因的老鼠的变老的肝被发现。TIMP-1 的 mRNA 和蛋白质表情在最年老的动物显著地高。组织病理学说的变化， mRNA 和 TIMP-1 的蛋白质表达式作为与正常鼠标相比在转基因的鼠标的肝显著地增加了。MMP-2and MMP-9 的表示在老化的过程显示出一个次要的变化。肝变化和骨胶原免职没在小老鼠被观察，但是草皮的活动减少了 P 【 0.05 ) ，并且毛(P【0.01 ) 的活动和 MDA 的内容在转基因的老鼠(P【0.01 ) 的肝增加了。TIMP-1 的结论 Theexpression 在在老化的进程的转基因的老鼠的肝显著地高，显示氧化水平增加，抗氧化的能力在转基因的老鼠的肝减少。TIMP-1 在肝老化的过程起一个重要作用。

英文摘要：

Background Tissue inhibitor of matrix metaUoproteinase-1 （TIMP-1） is related to the aging of many organs, but few data are available on the change of TIMP-1 in liver aging. The purpose of this study was to investigate the expression and role of TIMP-1, matrix metalloproteinase-2 （MMP-2） and MMP-9 in the process of natural aging in the livers of normal and transgenic mice, and to detect the effects of TIMP-1 on oxidative level and anti-oxidative ability of the livers of transgenic young mice. Methods Normal and transgenic mice were divided into 3 groups according to their age： 3-month-old group （n=5）, 12-month-old group （n=5） and 24-month-old group （n=5）. Histopathological changes of the liver were observed after HE and Masson staining. The messenger RNA （mRNA） levels of TIMP-1, MMP-2 and MMP-9 were determined by semi-quantitative reverse transcriptional polymerase chain reaction; protein expression was measured by Western blot in the livers of normal and transgenic mice of various ages. Changes in levels of superoxide dismutase （SOD）, monoamine oxidase （MAO）, malondialdehyde （MDA） as well as oxidative and anti-oxidative ability were measured. Results Histologically, more fatty degeneration and collagen deposition were found in the aging livers of transgenic mice than in those of the normal mice as their age of months increased. The mRNA and protein expressions of TIMP-1 were significantly high in the oldest animals. The histopathological changes, mRNA and protein expressions of TIMP-1 increased significantly in the liver of transgenic mice as compared with normal mice. The expression of MMP-2 and MMP-9 showed a minor change in the process of aging. Liver change and collagen deposition were not observed in young mice, but the activity of SOD decreased （P〈0.05）, and the activity of MAO （P〈0.01） and the content of MDA increased in the liver of transgenic mice （P〈0.01）. Conclusions The expression of TIMP-1 is significantly high in the liver of transgenic m

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