肝硬化门静脉高压TIPS术后血浆脂多糖变化对血小板释放血管内皮生长因子和血小板反应蛋白-1的影响

Effects of plasma lipopolysaccharide changes on platelet release of vascular endothelial growth factor and thromobospondin-1 in patients with cirrhotic portal hypertension after TIPS procedure

目的探讨肝硬化失代偿期门静脉高压患者经颈静脉肝内门体分流术(TIPS)后血浆脂多糖(LPS)浓度变化及其对血小板释放血管内皮生长因子(VEGF)和血小板反应蛋白(TSP)-1的影响。方法纳入肝硬化门静脉高压患者169例,其中81例接受TIPS治疗。检测不同Child-Pugh分级患者外周血浆LPS、VEGF及TSP-1浓度。在体外将正常人血小板与不同浓度LPS预孵育并使用胶原刺激后,检测血小板活化标志物(PAC-1)表达率以及释放VEGF和TSP-1浓度。检测TIPS患者术前术后血小板PAC-1表达率以及外周血浆LPS、VEGF和TSP-1浓度。分析TIPS术后患者血浆LPS、VEGF及TSP-1浓度变化与Child-Pugh评分变化的关系。据资料不同用t检验、单因素方差分析法或Pearson rho分析法进行统计学分析。结果Child-Pugh C级患者血浆LPS及TSP-1浓度均显著高于A、B级,但血浆VEGF浓度显著低于A、B级(P值均<0.01)。体外实验显示LPS浓度越高,血小板PAC-1表达率越高,上清液TSP-1浓度越高,但上清液VEGF浓度差异无统计学意义。TIPS术后患者门静脉压力及血小板活化程度均显著下降(P值均<0.01);术后血浆LPS及TSP-1水平持续显著下降,VEGF水平持续显著上升,而且血浆LPS浓度与TSP-1浓度呈正相关(r=0.506,P<0.001),与VEGF浓度呈负相关(r=-0.167,P=0.010)。TIPS术后Child-Pugh评分变化幅度与血浆VEGF浓度变化幅度呈负相关(r=-0.297,P=0.016),与血浆TSP-1浓度变化幅度呈正相关(r=0.145,P=0.031)。结论肝硬化门静脉高压TIPS术后门静脉梯度压力及血浆LPS浓度下降,相应血小板活化下降,若血小板释放TSP-1越少、释放VEGF越多,则有可能减少由门静脉血分流导致的肝功能损伤。

Objective To investigate the effects of plasma lipopolysaccharide(LPS)concentration changes on platelet release of vascular endothelial growth factor(VEGF)and thrombospondin(TSP)-l in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt(TIPS)procedure.Methods 169 cases with cirrhotic portal hypertension were enrolled,of which 81 cases received TIPS treatment.LPS,VEGF,and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured.After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro,platelet PAC-1 expression rate,VEGF,and TSP-1 concentrations were detected.PAC-1 expression rate and the concentrations of LPS,VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected.The relationship between plasma LPS,VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed.Statistical analysis was performed by t-test,one-way ANOVA or Pearson's rho according to different data.Results Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B,but the concentration of plasma VEGF was significantly lower than class A and B(/^<0.01).In vitro experiments showed that concentration of LPS,TSP-1,and platelet PAC-1 expression rate was higher in the supernatant,but the difference in the concentration of VEGF in the supernatant was not statistically significant.Portal vein pressure and platelet activation were significantly decreased(P<0.01)in patients after TIPS procedure.Portal venous pressure,platelet activation,plasma LPS,and TSP-1 levels were significantly decreased continuously,while VEGF levels were significantly increased continuously after TIPS procedure.Plasma LPS concentration was positively correlated with TSP-1 concentration(r=0.506,P<0.001),and negatively correlated with VEGF concentration(r=-0.167,P=0.010).Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration(r=-0.297,P=0.016),and positively correlated with change range of plasma TSP-1 concentration(r=0.145,P=0.031)after TIPS.Conclusion Portal venous pressure gradient,plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure,and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.