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 mouse in the process of aging, indicating that the oxidative level increases and the anti-oxidative ability decreases in the liver of transgenic mouse. TIMP-1 plays an important role in the process of liver aging.
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 mouse in the process of aging, indicating that the oxidative level increases and the anti-oxidative ability decreases in the liver of transgenic mouse. TIMP-1 plays an important role in the process of liver aging.
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)Postdoctor Foundation of China (No. 2004035048).
