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目的探讨金属蛋白酶抑制物-1(TIMP-1)及其金属蛋白酶(MMP)-2、MMP-9在TIMP-1转基因小鼠和正常小鼠肝脏自然衰老过程中的表达和作用。方法选择3、12和24月龄正常和TIMP-1转基因小鼠,采用HE和Masson染色,观察小鼠肝脏的组织病理学改变,用RT-PCR和Western blot法分别检测TIMP-1和MMP-2、MMP-9在不同月龄小鼠肝脏组织中的表达。测定3月龄小鼠肝脏中超氧化物歧化酶(SOD)、单胺氧化酶(MAO)活性及丙二醛含量。结果24月龄小鼠肝脏中有较多的脂肪变性和胶原沉积,TIMP-1的表达随小鼠月龄增加而增高,转基因小鼠的病变更明显。两组小鼠MMP-2和MMP-9的表达均无明显变化。3月龄转基因小鼠肝脏组织学结构和形态无明显改变,但SOD活性降低,MAO活性增高,丙二醛含量增高(P<0．05)。结论TIMP-1表达增高在肝脏衰老过程中可能起重要作用。
Objective To investigate the expression and role of TIMP-1, MMP-2 and MMP-9 in the natural aging of liver of TIMP-1 transgenic mice and normal mice. Methods The normal and TIMP-1 transgenic mice were selected at 3, 12 and 24 months of age and the histopathological changes of liver were observed by HE and Masson staining. The expressions of TIMP-1 and MMP- The expression of MMP-9 in liver tissue of different age mice. The activities of superoxide dismutase (SOD), monoamine oxidase (MAO) and malondialdehyde (MDA) in the liver of 3-month-old mice were determined. Results There was more steatosis and collagen deposition in the liver of 24-month-old mice. The expression of TIMP-1 increased with the increase of the age of the mice. The lesions in the transgenic mice were more obvious. There was no significant change in the expression of MMP-2 and MMP-9 between the two groups of mice. The liver histology and morphology of 3-month-old transgenic mice showed no significant changes, but SOD activity decreased, MAO activity increased, and malondialdehyde content increased (P <0.05). Conclusion The increased expression of TIMP-1 may play an important role in the process of liver aging.