The Change Of Plasma LPS Level And It's Effect On Platelet Release Of VEGF And TSP-1 In Patients With Cirrhosis And Portal Hypertension After TIPS

BackgroundThe common complications of liver cirrhosis and portal hypertension include esophageal-gastric varices and refractory ascites,which is one of the major causes of death in patients with cirrhosis.At present,the treatments provided by relevant guidelines are mostly based on internal medicine.However,transjugular intrahepatic portosystemic shunt(TIPS)has gradually become one of the effective treatments for complications related to portal hypertension in cirrhosis in recent years.A stent shunt was established between portal vein and hepatic vein between the hepatic to make the blood from portal vein directly shunt to the vena cava5 which plays a role in reducing portal pressure.Although TIPS is effective in treating complications of portal hypertension in patients with cirrhosis,its clinical application remains controversial because postoperative liver injury and hepatic encephalopathy have not improved patient survival.Shunt in reducing the pressure of the portal vein will inevitably reduce intrahepatie perfusion and damage liver function.How to increase intrahepatic perfusion and improve the liver function of patients with cirrhosis is the major problem to be solved after the treatment of cirrhosis and portal hypertension with TIPS.Previous studies have reported that platelet activation and release of cytokines can affect liver function and cirrhosis,and platelet activation release of vascular endothelial growth factor(VEGF)may be beneficial to liver function,and Thrombospondin-1(TSP-1)may damage liver function.In addition,cirrhotic portal hypertension can increase the concentration of lipopolysaccharides(LPS)in peripheral blood,which plays a key role in platelet activation in cirrhotic patients with portal hypertension.TIPS can effectively reduce portal pressure,and LPS levels will change with the decline in portal pressure,thereby affecting platelet activation and release.PurposeThis study was mainly to analyze the correlation between plasma LPS,VEGF and TSP-1 levels and liver function in cirrhotic patients with decompensated portal hypertension.At the same time,this study focused on whether TIPS can reduce portal pressure and liver LPS Level to change the activation of platelet and its related particles or release of VEGF and TSP-1,thus affecting liver function of the patients.Materials and MethodsThls study included 169 patients with cirrhosis and portal hypertension(81 patients undergoing TIPS),and 20 healthy controls.(1)The levels of LPS,VEGF and TSP-1 from patients with cirrhosis in different Child-Pugh classification were detected by enzyme-linked immunosorbent assay(ELISA).(2)Normal human platelets were pre-incubated with different concentrations of LPS and stimulated by collagen in vitro.The CD62P and PAC-1 expression,VEGF and TSP-1 levels were detected by flow cytometry and ELISA respectively.(3)Flow cytometry was used to detect the preoperative and postoperative platelet CD62P and PAC-1 expression and plasma platelet microparticles(PMPs)in 31 patients with TIPS.(4)ELISA was used to detect the the preoperative and postoperative levels of LPS,VEGF,and TSP-1 in peripheral plasma of 50 patients with TIPS.(5)Analyze the relationship between the changes of plasma LPS,VEGF,TSP-1 levels and liver function after TIPS.Results1.Patients with different stages of Child-Pugh cirrhosis with portal hypertension had significantly different levels of plasma LPS,VEGF,TSP-1 and platelet counts.The levels of plasma LPS and TSP-1 in Child-Pugh C group were significantly higher those in Child-Pugh class A and B patients(P<0.01),while the levels of plasma VEGF and platelet counts in Child-Pugh C patients were significantly lower than those in Child-Pugh A and B patients(P<0.01).The levels of plasma LPS,VEGF and TSP-1 and platelet counts were correlated with Child-Pugh seores in patients with cirrhosis and portal hypertension.2.In vitro experiment:the higher concentration of LPS caused the higher expression rate of platelet CD62P and PAC-1,and the higher concentration of TSP-1 secreted by platelets.But there was no significant difference in VEGF secreted by platelets.3.The portosystemic gradient,level of plasma LPS and the expression of CD62P and PAC-1 from platelets and plasma PMPs significantly decreased after TIPS(P<0.01).4.The levels of LPS and TSP-1 in plasma of patients with decompensated cirrhosis and portal hypertension were transiently increased significantly at 7 days after TIPS,but decreased significantly after one month and were significantly lower than those before operation.There was no signifieant change in plasma VEGF concentration at 7 days after TIPS in patients with decompensated portal hypertension but persisted after one month and was significantly higher than preoperative levels.Among them,the change of plasma LPS level was positively correlated with plasma TSP-1 level,and negatively correlated with plasma VEGF level.5.The more increase in VEGF and more decrease in TSP-1,the less increase in Child-Pugh score after TIPS,ConclusionsThe levels of plasma LPS,VEGF and TSP-1 in patients with cirrhosis and portal hypertension were correlated with liver function.LPS and TSP-1 were negative and VEGF was positive.Ii patients with cirrhosis and portal hypertension,portal vein pressure and plasma LPS concentration decreased after TIPS,which would cause the decrease of platelet activation and the release of TSP-1,but the increase of VEGF,resulting in the activation and release of platelet from preoperative damage the state of liver function is changed to protect liver function state after operation.