The Effect Of EPCs In Portal Hypertension And Cirrhosis Pathogeny And Treatment

Objective:In order to reveal the relationship between endothelial progenitor cells(EPCs)and liver cirrhosis(LC)and portal hypertension(PTH),we detect the number,proliferation,migration,adhesion function of rat bone marrow EPCs in normal group,compensatory phase of liver cirrhosis group and Portal Hypertension group,respectively.We also investigate the perindopril(angiotensin converting enzyme inhibitor,ACEI)therapeutic action on PTH and the effect on the number,proliferation,migration,adhesion function of EPCs.Methods:Adult male SD rats weighting 180-210 g were used in this study.The rats had access to food and water ad libitum and were housed within a room with a 12:12 h dark-light cycle.All the animals were randomly divided into five groups(n=20).Group 1 is normal group.Group 2 and 3 are compensatory phase of liver cirrhosis group and Portal Hypertension group.Group 4 and 5 are ACEI group and the control group.In group 2 to 5,we use carbon tetrachloride rapeseed oil,ethanol and high fat diet feeding diet to product rat model with liver cirrhosis and liver cirrhosis portal hypertension.The concentration of carbon tetrachloride rapeseed oil is 0.3 ml/100 g with dose-dependence.As control group,rats in group 1 get normal rapeseed oil,water and normal feed.We use fully automatic biochemical analyser to detect the rat serum ALT(Alanine aminotransferases),AST(Aspartate aminotransferase),ALT/AST,TBIL(Total Bilirubin),DBIL(Direct Bilirubin),IBIL(Indirect Bilirubin),TP(Total Protein),ALB(Albumin),GLO(Globulin)in groups 1 to 3.In order to determine whether building success,we measure of portal vein pressure and observe the liver shape variation of rats in groups 1 to 3.The rats in group 4 are lavage with perindopril 10 mg/kg/d.At the same time,the rats in group 5 are lavage with water.EPCs are cultivated by the method of enzyme digestion associating with tissue adhere from bone marrow.After that,we detect the proliferation,migration,adhesion function of EPCs using flow cytometry,MTT,improved Boyden chamber method.The data are reported as means ± standard errors of the means(SEMs)using SPSS 16.0 for Windows.Differences between groups are analyzed by one-way analysis of variance(ANOVA);correlation is analyzed by linear correlation;p-values<0.05 were considered significant.Results:1.Liver function index:(1).ALT,AST,TBIL and GLO in group 2,3 are at higher level than that in group 1(P<0.05).The levels of this function index in group 3 are also higher than that in group 2(P<0.05).(2):ALB in group 2,3 are at lower level than that in group 1(P<0.05).In group 3 the ALB is also lower than that in group 2(P<0.05).2.Portal venous pressure:Significant higher portal venous pressure in group 2,3 compare to that in group 1(P<0.05).The portal venous pressure in group 3 is at higher level than that in group 2(P<0.05).There is also no statistically significant difference among the group 1,4 and 3,5(P>0.05).3.Pathologic change in hepatic tissue:(1).Macropathology:In group 1,the liver volume,quality and capsule are normal.The surface and section of the liver are smooth.But in group 2,the liver volume gets larger and the quality becomes firmer.Similar to the size of the nodules appear and the capsule thicken.Interestingly,the liver volume lessens and the quality hardens in group 3.Surface and section diffuse Similar to the size of the nodules.The liver weight in group 2 is the heaviest.The group 1 weight is heavier than that in group 3(P<0.05).(2).Light microscope:In group 1,there is normal hepatocytes and central veins without abnormal hepatocytes in liver.But Liver tissue fibroplasia and pseudolobule emerge in group 2.In the pseudolobule hepatocytes get irregular arrangement or deformation or necrosis with Lymphocytes and monocytes.In group 3,liver suffuses pseudolobule with fibrous tissue hyperplasia extensively.There is also irregular arrangement hepatocyte which is deformation or necrosis.4.The number of EPCs and the function of proliferation,migration,adhesion:There is no statistically significant difference among the group 1,4 and 3,5(P>0.05).These indexes in group 1 are better than these in group 2 and 3(P<0.05).The group 2 is better than the group 3(P<0.05).5.Linear correlation analysis:There is significant negative correlation between the number of EPCs,and the proliferation,migration,adhesion function of EPCs and portal venous pressure linear correlation analysis.Conclusion:1.One of the cirrhotic portal hypertension pathogenesis is the number,proliferation,migration,adhesion functions of EPCs reduced.2.Perindopril could lessen portal vein pressure and improve the proliferation,migration,adhesion functions of EPCs.Perindopril should be the tendency in the liver cirrhosis and portal hypertension treatment strategies.