Clin Sci (Lond). 2014 May;126(9):633-44. doi: 10.1042/CS20130215.
Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-1α, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.
肝硬化中的异常血管生成常导致严重并发症,如静脉曲张出血和肝性脑病。此外,内脏血管生成会升高门静脉压力,而血管生成因子在其中发挥关键作用。绿茶多酚(GTP)从茶树中提取,具有抗血管生成特性,但尚未研究其在肝硬化上述参数中的作用。本研究旨在确定 GTP 在肝硬化中的作用,并探讨其潜在机制。通过胆总管结扎法(BDL)在 Spraque-Dawley 大鼠中诱导肝硬化。它们随机接受 GTP 或 DW(蒸馏水,载体)治疗 28 天,然后评估血流动力学参数、门体分流、肠系膜窗血管密度、肝内血管生成、肝纤维化、血浆 VEGF(血管内皮生长因子)浓度、肠系膜血管生成因子和受体蛋白表达以及血清和肠系膜氧化应激参数。与 DW 组相比,GTP 显著降低了门体分流、肝纤维化、肝内血管生成、肠系膜窗血管密度、VEGF 浓度,并下调了肠系膜 HIF(缺氧诱导因子)-1α、VEGF 和磷酸化 Akt 的表达。总之,GTP 通过抑制 HIF-1α、Akt 激活和 VEGF 改善门体分流和肠系膜血管生成的严重程度。GTP 似乎是一种通过抗血管生成控制与门静脉高压相关并发症的合适药物。