摘要
目的:观察缺氧诱导因子-1α(HIF-1α)及其下游分子VEGF基因在酒精性肝病大鼠肝组织中的表达,分析它们与酒精性肝病发生发展的关系。方法:以白酒-玉米油-吡唑混合液灌胃14周建立酒精性肝病动物模型,常规HE和Masson染色动态观察4、8、14周时肝组织脂肪变程度和炎症程度的变化;XOD法检测血清SOD活性,TBA法检测血清MDA含量;ELISA法检测肝组织中TNF-α含量;RT-PCR技术动态检测肝组织HIF-1α及其下游分子VEGF mRNA的表达。结果:随着饮酒时间的延长大鼠血清MDA含量和肝组织TNF-α水平、HIF-1αmRNA和VEGFmRNA表达逐渐增加,血清SOD活性逐渐降低,同时肝组织脂肪变程度和炎症程度逐渐加重;在造模4周,血清MDA和SOD水平、肝组织TNF-α含量、HIF-1αmRNA和VEGFmRNA表达与正常组差异无显著性(P>0.05);在造模8周MDA和TNF-α含量较正常组明显增高、SOD活性较正常组明显降低(P<0.01、P<0.05),HIF-α、VEGF mRNA表达较正常组有增高趋势,但差异无显著性;至造模14周时MDA和TNF-α含量、HIF-1α和VEGF mRNA表达均较正常组及模型4周组显著增高(P<0.01、P<0.05),SOD活性则明显降低;相关性分析显示,HIF-1αmRNA表达水平与肝组织脂肪变程度、炎症程度、VEGFmRNA表达、TNF-α含量及血清MDA水平均呈明显的正相关,而与血清SOD活性呈明显的负相关(P<0.01、P<0.05)。结论:HIF-1α及其下游因子VEGF参与酒精性肝病的发生发展。
Objective：To observe the expression of hepatic hypoxia inducible factor-1α（HIF-1α） and its downstream Molecules VEGF gene in rat with alcoholic liver disease,and to clarify the relationship between alcoholic liver disease and them.Methods：The model of alcoholic liver disease in rats could be established by dealing with the mixture of alcohol,corn oil,and pyrazole inr 14 weeks.With HE and Masson staining to dynamically observe the degree of liver steatosis and inflammation at the end of 4 8 14th week,and with XOD method to detect serum SOD,TBA method to detect the content of serum MDA,ELISA to test the hepatic TNF-α,The expression of HIF-1α and its downstream molecules VEGF mRNA were detected dynamically with RT-PCR.Results： With the prolonging of drinking time,the content of serum MDA and the level of hepatic TNF-α and the expression of the hepatic HIF-1α and its downstream molecules VEGF gene were gradually increased,on the contrary,the activity of serum SOD was gradually declined,at the same time,the degrees of hepatic steatosis and inflammation were further severe.The expression of HIF-1α and VEGF mRNA and the content of hepatic TNF-α and the levels of the serum SOD and MDA had not remarkable difference at the end of the 4th week in the model group rats（P﹥0.05）,the content of the serum MDA and hepatic TNF-α in the model rats were higher than that in normal group at the end of the 8th week,but the serum SOD was significantly lower than those in the normal group（P 0.01,P 0.05）.Compared with the rats in the normal,the expression of HIF-1α and VEGF mRNA in the model showed the tendency of increase but no significant difference,The expression of hepatic HIF-1α and VEGF mRNA and the content of serum MDA and hepatic TNF-α at the end of 14th week were higher than those in normal and at the end of 4th week,on the contrary,the activity of serum SOD was decreased,（P0.01,P0.05）Correlation analysis showed the Expression of HIF-1α was positively correlated with the degree of hepatic steatosis and inflammation,the content of serum MDA,the level of hepatic TNF-α and VEGF mRNA,but negatively correlated with the activity of serum SOD.Conclusion： HIF-1α and its downstream molecules VEGF mRNA take part in the development of alcoholic liver disease.
出处
《中华中医药学刊》
CAS
2010年第12期2535-2538,共4页
Chinese Archives of Traditional Chinese Medicine
基金
浙江省中医药科技计划资助项目(2007YA009)
关键词
酒精性肝病
缺氧诱导因子-1Α
血管内皮生长因子
alcoholic liver disease
hypoxia inducible factor-1α
vescular endothelial growth factor
