肝硬化门脉高压性胃病差异表达蛋白的筛选及功能鉴定

Screening and functional identification of differentially expressed proteins in liver cirrhosis with portal hypertensive gastropathy

目的寻找门脉高压性胃病(portal hypertensive gastropathy,PHG)患者与正常人胃黏膜之间差异表达蛋白,并探索这些蛋白参与的功能及信号通路。方法选取5例肝硬化PHG患者及5名健康志愿者,在胃镜下钳取胃黏膜组织,通过非标定量技术以及基于质谱的定量蛋白质组学技术进行定量比对,寻找差异表达蛋白,并对其进行生物信息学分析,且选取差异表达最明显的蛋白,通过平行反应监测(parallel response monitoring,PRM)进行验证。结果共筛选出178个差异表达蛋白,其中上调蛋白84个,下调蛋白94个,它们主要参与补体和凝血级联反应通路。而上调蛋白Tenascin和Elastin参与间质增生、调节血管平滑肌增生和结构塑造等,下调蛋白Haptoglobin和Coagulation factorⅫ则参与肝脏回收血红素铁、抗氧化、凝血和纤溶反应等。结论肝硬化PHG患者与健康人相比,其胃黏膜上存在多种差异蛋白,这些蛋白参与了肝硬化及PHG的病理生理过程。

Objective To find the differentially expressed proteins in gastric mucosa between patients with portal hypertensive gastropathy(PHG)and normal controls,and to explore the functions and signaling pathways involved in these proteins.Methods Five liver cirrhosis patients with PHG and 5 heathly colunteers were selected.Gastric mucosa tissue was extracted under gastroscope by non-standard quantitative technique and quantitative proteomics technique based on mass spectrometry.Quantitative comparison was conducted to find differentially expressed proteins,and bioinformatics analysis was performed on them.The most obvious differentially expressed proteins were selected and verified by parallel response monitoring(PRM).Results 178 differentially expressed proteins were selected,including 84 up-regulated proteins and 94 down-regulated proteins,which were mainly involved in complement and coagulation cascades pathway.Among the up-regulated proteins,Tenascin and Elastin were involved in extracellular matrix protein composition and proliferation and organization of vascular smooth muscle,while the down-regulated proteins Haptoglobin and coagulation factor Ⅻ were involved in hepatic recycling of heme iron,antioxidant,coagulation and fibrinolysis,etc.Conclusion Multiple differentially expressed proteins in gastric mucosa of cirrhotic patients with PHG are screened,and these proteins are involved in the pathophysiological process of liver cirrhosis and PHG.