Relationship Between Serum Endothelin 1,Angiotensin Ⅱ And Portal Hypertension In Cirrhotic Patients

Part I:Relationship between hepatic venous pressure gradient(HVPG)and serum ET-1 and Ang-II levels in patients with cirrhosisObjective:to analyze the relationship between hepatic venous pressure gradient(HVPG)and serum ET-1 and Ang-Ⅱ in cirrhotic patients.Methods:from Jan 2017 to Dec 2017,120 patients with cirrhosis were examined by HVPG in our department of Gastroenterology.According to the HVPG value,the group was divided into<10mmHg group(HVPG value<10mmHg)and 10mmHg group(HVPG value was greater than 10mmHg).The clinical characteristics of the two groups and the difference of serum ET-1 and Ang-Ⅱ levels were compared.The effects of HVPG on the patients with liver cirrhosis were analyzed,and the relationship between HVPG and serum ET-1 and Ang-Ⅱ was analyzed.Results:among the 120 patients,47 patients with HVPG<10mmHg were included in group 10mmHg,and those in group 10mmHg73 were more than 10mmHg.The proportion of B and C grade and the MDCT score of the submucosal vein of the esophagus were 2-3 points higher than that of the 10mmHg group,and the serum ET-1 and Ang-Ⅱlevels were significantly higher than those in the<10mmHg group(P<0.05).The results of Logistic regression analysis showed that after liver cirrhosis,combined ascites,liver function Child-pugh classification,MDCT score of submucosal vein,serum ET-1 and serum Ang-Ⅱ level were all the factors influencing the increase of HVPG in patients with liver cirrhosis(P<0.05).Conclusion:the clinical features of patients with liver cirrhosis were taken as dependent variables,and the HVPG was elevated to the independent variable and replaced by Logistic regression equation The results showed that liver cirrhosis,combined ascites,Child-pugh classification of liver function,MDCT score of submucosal vein,serum ET-1,and serum Ang-Ⅱwater were the influence factors of the elevation of HVPG in the patients with cirrhosis.P<0.05,Part Ⅱ:The expression of endothelin-1 and angiotensin-II in cirrhotic portal hypertension before and after treatmentThe expression of endothelin-1 and angiotensin-Ⅱ in cirrhotic portal hypertension before and after treatment.Methods:60 healthy Wister male rats were randomly divided into control group(group A),liver cirrhosis portal hypertension group(group B),bosentan group(group C),losartan group(D group),and Kato Pury group(group E),each group was 12.In group B,C,D and E,the rat model of liver cirrhosis with portal hypertension was established by CCl4 and phenobarbital.The liver tissues of each group were stained with HE,Massion and portal pressure to judge the formation of the model.The serum ET-1 and Ang-Ⅱ levels of the portal vein were detected in each group,and the HE and Massion staining of the portal vein was carried out,and the immunization was adopted.The expression of NF-kappa B and TGF-beta in the portal vein was detected by histochemistry.The expression of VEGF mRNA was detected by in situ hybridization,and the relative expression of type Ⅰ and type Ⅲ procollagen mRNA was detected by Rt-PCR.Result:(1)the modeling of portal hypertension in liver cirrhosis:(1)most of the animals in group B,C,D and E were gradually reduced in the course of induction,poor spirit,poor appetite,drinking water 20-25ml every day,slow reaction,glossy skin,different degrees of ascites and weight loss.The number of surviving rats was 12 in group A,8 in group B,9 in group C,8 in group D,and 10 in group E.HE staining showed that the structure of liver lobules in group A was complete,the hepatic cord arranged well and the liver cells were normal,and the structure disorder of the model group(group B,C,D,E)formed false lobule,the interlobular bile duct hyperplasia,and a large number of inflammatory cells invaded.Masson staining:there was no fibrous tissue hyperplasia in the portal area of group A,and a small number of reticular fibers were seen in the central vein of the liver and in the hepatic sinusoid.The fibrous tissue of the model group(B,C,D,E)is widely proliferated and a large number of inflammatory cells infiltrate,destroying the normal structure of the hepatic lobule,and dividing it into a small,round or round like liver cell group,forming false lobule and small nodular liver cirrhosis,but the regeneration of the hepatocytes is not obvious.The portal pressure of model group(B,C,D,E group)was significantly higher than that of A group,and portal pressure of C,D and E group was significantly lower than that of B group(P<0.05).(2)visible to the naked eye,portal vein of model group(B,C,D and E)was thicker than that of A group.HE,Massion staining:the endometrium of group A is thinner and the middle membrane is composed of a few layers of loose ring smooth muscle.The outer membrane is thicker and is composed of connective tissue and often contains more longitudinal smooth muscle bundles.The model group(group B,C,D,E)is diffuse or partial thickening,containing a large number of smooth muscle cells and collagen fibers;local hyperplasia is hilly.A small thrombus was formed on the surface of the damaged vascular endothelium;the smooth muscle cells of the middle membrane were proliferated and hypertrophy,and the muscle fibers were thickened and dense,and some of them protruded to the intima.(2)immunohistochemical dataThe expression level and intensity of NF-kappa B and TGF-beta in group B,C,D and E were all higher than that of A group(P<0.05),while C,D,E groups were lower than those in the group,and the level of expression,intensity and integral light density were lower than those in the group.(3)the results of in situ hybridizationThe normal portal vein in the A group had less VEGF mRNA expression,while the portal vein VEGFmRNA expression level in B,C,D and E increased significantly(P<0.05),and the positive cell number and the integral light density of B,C,D,and other groups were significantly higher than those in the group.Group D(P<0.05).(4)Rt-PCR results:the expression of type I and type III procollagen mRNA in the portal vein of the model group(B,C,D,E)was significantly higher than that in the A group.The mRNA expression of type Ⅰ and Ⅲ procollagen in the portal vein of C,D and E was significantly lower than that of the B group.(5)the comparison of serum ET-1 and Ang-Ⅱ levels in all groupsThe level of serum ET-1 and Ang-Ⅱ in the portal vein of the model group(B,C,D,E)was significantly higher than that in the A group.The level of serum ET-1 in the portal vein of D and E was significantly lower than that in the B group and the C group.Conclusion:ET-1 and Ang-II participate in the regulation of the formation of smooth muscle cells and extravascular matrix through interaction,and Ang-II can promote the synthesis of ET-1 in vascular smooth muscle cells.ET-1 and Ang-II are involved in the occurrence and progression of cirrhosis with portal hypertension.6)Comparisons of portal vein pressure in each groupThe level of portal vein pressure in model group(group B,C,D,E)was significantly higher than that in group A.The level of portal vein pressure in group C,D and E was significantly lower than that in group B(P<0.05).