RESUMEN
OBJECTIVE: To investigate the gene differential expression patterns in hepatocirrhosis and non-hepatocirrhosis tissues within different ischemic time. METHODS: The liver tissues were divided into two groups: Group A (non-hepatocirrhosis), Group B (hepatocirrhosis), each of which consisted of 3 groups with different ischemic time: 15, 30 and 45 minutes. The gene differential expression patterns in the two groups within different ischemic time were detected and compared with those in normal liver tissues by using 4000 points gene microarray. RESULTS: In non-hepatocirrhosis tissues, the homeostatic maintenance genes expressed highly during hepatic ischemia for 15 minutes, and no apoptotic gene was expressed; but in hepatocirrhosis tissues, many apoptotic genes expressed highly. As for 30 minutes, in both two groups liver tissue genes expressed to the peak, and the genes related to cell death, oxidative stress and nuclear factors expressed highly. The difference lies in the facts that in Group B pro-apoptosis genes expressed more than those in Group A, and the Ratio values were higher than those in Group A. Many genes of heat shock protein family and antioxidant proteins expressed highly simultaneously in Group A, but comparatively low in Group B. As for 45 minutes, genes of heat shock proteins and antioxidant proteins expressed lowly in Group B. CONCLUSIONS: It suggests that the safe time limit of hepatic ischemia for cell survive is 30 minutes or so. Non-hepatocirrhosis tissues could endure 30 minutes of ischemia and even longer, but it should be restricted within 30 minutes in hepatocirrhosis tissues.
Asunto(s)
Perfilación de la Expresión Génica , Isquemia/genética , Cirrosis Hepática/genética , Hígado/irrigación sanguínea , Humanos , Hígado/metabolismo , Cirrosis Hepática/patología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Factores de TiempoRESUMEN
AIM: To investigate the multiple gene differential expression patterns in human ischemic liver and to produce the evidence about the hepatic ischemic safety time. METHODS: The responses of cells to hepatic ischemia and hypoxia at hepatic ischemia were analyzed by cDNA microarrary representing 4 000 different human genes containing 200 apoptotic correlative genes. RESULTS: There were lower or normal expression levels of apoptotic correlative genes during the periods of hepatic ischemia for 0-15 min, the maintenance homostatic genes were expressed significantly higher at the same time. But at the hepatic ischemia for 30 min, the expression levels of maintenance homeostatic genes were down-regulated, the expressions of many apoptotic correlative genes and nuclear transcription factors were activated and up-regulated. CONCLUSION: HIF-1, APAF-1, PCDC10, FBX5, DFF40, DFFA XIAP, survivin may be regarded as the signal genes to judge the degree of hepatic ischemic-hypoxic injure, and the apoptotic liver cell injury due to ischemia in different time limits. The safe limit of human hepatic warm ischemic time appears to be generally less then 30 min.