Dynamic Alteration Of NOX4 And Ang?/Ang-(1-7) Ratio In Experimental Liver Fibrosis

Objective:To investigate the dynamic changes of the NOX4 and Ang?/Ang-(1-7)during experimental liver fibrosis,in order to clear the correlation between liver fibrosis and oxidative stress,and Ang ? and Ang-(1-7)effect on liver fibrosis by oxidative stress,to further explore the pathogenesis of hepatic fibrosis and their significance in the pathogenesis of hepatic fibrosis.To provide new ideas for the prevention and treatment of hepatic fibrosis in clinic.Methods:34 SD male rats(190-210)g] were randomly divided into 2 groups: normal control group(n = 6)and model group(n = 28).The rats in the model group were given subcutaneous injections with 40% CCL4,twice a week.The first subcutaneous injection of 5ml/kg,after 2ml/kg.At the same time,the control group was injected with the same dose of oil.All rats were given daily diet.At the end of two,four,six,and eight,respectively,the rats of model group were sacrificed,and the liver tissue of the same site was reserved for the first time.In the model group,the rats in the normal group were killed at the end of the eight week,and the liver tissue was taken for experiment.The liver tissue of rats with conventional HE and Masson trichrome staining to observe the pathological changes in liver tissue,The concentration of Ang?and Ang-(1-7)was determined by enzyme linked immunosorbent assay,then calculate the ratio of Ang ?/Ang-(1-7),the expression of NOX4 mRNA in liver was determined by Real-timePCR method.Results:(1)pathological changes:compared with control group,the liver cells inflammation were obviously and hepatic fibrosis were gradually formation and increased along with the days after experiment in model group.(2)ELISA determination results showed that:the results showed that,compared with the control group,the Ang?/Ang-(1-7)ratio were gradually increased in model groups(0.65±0.06?0.66±0.07?0.79±0.07?0.82±0.04),which had significant difference comparing with that in control group(0.59±0.04),respectively,P<0.05;(3)Real-timePCR results showed that:With the formation of liver fibrosis,the expression of NOX4 mRNA in model group were 6.53±0.89?5.49±1.24?14.49±2.39?31.78±3.96,which were obviously higher than that in normal groups(2.03±0.31),respectively,P<0.05;(4)correlation analysis showed that There was a positive correlation between the level of NOX4 mRNA and Ang?/Ang(1-7)ratio(r=0.901,P<0.05).Conclusion:(1)In the process of hepatic fibrosis,NADPH Oxidase 4(NOX4)mRNA expression were gradually increased.at the same time,the ratio of Ang ? /Ang-(1-7)in liver homogenate increased gradually.(2)NOX4 and Ang ? /Ang-(1-7)ratio change is positive related.(3)Ang ? and Ang-(1-7)may be involved in the occurrence and development of hepatic fibrosis with over regulation of oxidative stress.