Abstract：
Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow\'s triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.
摘要：
肝硬化门静脉血栓形成（PVT）的病理生理学仍未完全了解。门静脉循环中脂多糖（LPS）水平升高与高凝显著相关，增加血小板活化和内皮功能障碍。该研究的目的是调查LPS是否与门静脉血流减少有关。Virchow三合会的第三个组成部分，以及潜在的机制。血清亚硝酸盐/硝酸盐，作为一氧化氮（NO）生成的标志，在20例接受经颈静脉肝内门体分流术（TIPS）的肝硬化患者的门静脉和体循环中测量了LPS；在每位患者中还测量了门静脉血流速度（PVV），并与NO和LPS水平相关。与体循环相比，门静脉中的血清亚硝酸盐/硝酸盐和LPS显着升高；LPS与血清亚硝酸盐/硝酸盐之间存在显着相关性（R=0.421；p<0.01）。TIPS前后的PVV中位数为15cm/s（6-40）和31cm/s（14-79），分别。PVV与NO和LPS的相关性分析显示PVV与门静脉NO浓度呈显著负相关(R=-0.576;p=0.020),但不是LPS。内皮细胞的体外研究表明，LPS增强内皮NO的生物合成，被L-NAME抑制了，一氧化氮合酶的抑制剂，或TAK-242，TLR4，LPS受体的抑制剂；这种作用是通过上调eNOS和iNOS来实现的。研究表明，在肝硬化中，内毒素血症可能是通过NO和，因此,为PVT的发展做出贡献。
