摘要
目的金属蛋白酶组织抑制因子(TIMPs)具有抑制金属蛋白酶(MMPs)的作用,为了阐明TIMP-1和TIMP-2在肝硬变患者肝组织中的表达水平及分布状态。我们检测了肝硬变患者肝组织中的TIMP-1和TIMP-2,探讨TIMP-1和TIMP-2在肝硬变发病机制中的作用。方法以TIMP-1和TIMP-2 cDNA探针为试剂。采用原位杂交技术检测40例经肝组织病理学检查证实为结节性肝硬变患者肝组织中(其中男32例.女8例,平均年龄为50岁)TIMP-1和TIMP-2 mRNA的表达。结果 40例肝硬变患者肝组织中TIMP-1利TIMP-2 mRNA表达的阳性率为100％,TIMP-1 mRNA的表达强阳性40例中有32例,占80％,中等阳性6例,占15％.弱阳性2例,占5％;TIMP-2 mRNA的表达强阳性40例中有22例。占55％,中等阳性16例,占40％,弱阳性2例,占5％TIMP-1 mRNA阳性的肝组织中TIMP-2 mRNA亦为阳性,且TIMP-1 mRNA表达强度略高于TIMP-2 mRNA。而正常肝组织中未见阳性表达。TIMP-1利TIMP-2 mRNA表达的阳性信号主要位于肝细胞胞质中,未见细胞核表达。结论肝硬变患者肝组织中的肝细胞中存在TIMP-1和TIMP-2 mRNA的表达,TIMP-1和TIMP-2可能与肝病的进展相关,它通过抑制MMPs的活性,使得ECM降解减少而导致肝纤维化,以至肝硬变。
AIM To investigate the distribution of tissue inhibitors of metalloproteinase-1 and-2 (TIMP-1 and TIMP-2) in liver cirrhosis tissue and its relationship with the function of TIMP-1 and TIMP-2 in pathogenesis of liver cirrhosis. METHODS The subjects were 40 patients (32 male, 8 female) with liver cirrhosis. The liver TIMP-1 and-2 concentration was determined by in situ hybridization in liver tissues. RESULTS As compared with the controls (n=10), the liver TIMP-1 and-2 mRNA was increased in the 40 liver cirrhosis patients. The liver TIMP-1 and TIMP-2 mRNA were closely correlated with the histological degrees of liver cirrhosis. All were positive among the 40 samples. Expressions of TIMP-1 mRNA were high in 32, moderate in 6 and low in 2 patients. The rate was 85%, 15% and 5%, respectively. Expressions of TIMP-2 mRNA were high in 22, moderate in 16 and low in 2 patients. The rate was 55%, 40% and 5% respectively. Expressions of TIMP-1 and TIMP-2 were both positive, and expression of TIMP-1 was higher than TIMP-2. No expression was found in normal liver. Positive signal of hybridization was only seen in the cytoplasm. CONCLUSION Liver TIMP-1 and TIMP-2 concentrations may be increased with progression of the liver disease. The decreased degradation of extracellular matrix proteins, may result in the development of liver fibrosis and liver cirrhosis.
出处
《世界华人消化杂志》
CAS
2001年第3期251-254,共4页
World Chinese Journal of Digestology
基金
中国博士后科学基金资助项目
中博基[1999]10号
关键词
肝硬化
病理学
金属蛋白酶
组织抑制剂
金属蛋白酶2组织抑制剂
代谢
liver cirrhosis/pathology
tissue-inhibitor of metalloproteinase-1/metabolism
tissue-inhibitor of metalioproteinase-2/metabolism
RNA, messenger/metabolism
in situ hybridization
digoxin
