番茄红素治疗可改善胆汁性肝硬化大鼠肝内纤维化，并减轻病理性血管生成。

Lycopene treatment improves intrahepatic fibrosis and attenuates pathological angiogenesis in biliary cirrhotic rats.

机构信息

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.

Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2022 Apr 1;85(4):414-420. doi: 10.1097/JCMA.0000000000000699.

DOI:10.1097/JCMA.0000000000000699

PMID:35120355

Abstract

BACKGROUND

Liver cirrhosis is characterized by liver fibrosis and pathological angiogenesis, which results in hyperdynamic circulation, portal-systemic collateral vascular formation, and abnormal angiogenesis. Lycopene is a nutrient mostly found in tomatoes. The beneficial effects of lycopene include anti-inflammation, anti-oxidation, anti-fibrosis, and anti-angiogenesis; however, the association between liver cirrhosis and pathological angiogenesis has yet to be studied. This study aimed to investigate the effects of lycopene on biliary cirrhotic rats.

METHODS

The efficacy of lycopene treatment in common bile duct ligation (BDL)-induced biliary cirrhotic rats was evaluated. Sham-operated rats served as surgical controls. Lycopene (20 mg/kg/day, oral gavage) or vehicle was administered to BDL or sham-operated rats for 4 weeks, after which the hemodynamics, liver biochemistry, portal-systemic shunting, liver and mesenteric angiogenesis, and hepatic angiogenesis-related protein expressions were examined.

RESULTS

Lycopene alleviated hyperdynamic circulation as evidenced by decreased cardiac index and increased peripheral vascular resistance (p < 0.05), but it did not affect portal pressure or liver biochemistry in the BDL rats (p > 0.05). Lycopene significantly diminished the shunting degree of portal-systemic collaterals (p = 0.04) and mesenteric vascular density (p = 0.01), and also ameliorated intrahepatic angiogenesis and liver fibrosis. In addition, lycopene upregulated endothelial nitric oxide synthase, protein kinase B (Akt) and phosphatidylinositol 3-kinases (PI3K), and downregulated vascular endothelial growth factor receptor 2 (VEGFR-2) protein expressions (p < 0.05) in the livers of the BDL rats.

CONCLUSION

Lycopene ameliorated liver fibrosis, hyperdynamic circulation, and pathological angiogenesis in biliary cirrhotic rats, possibly through the modulation of intrahepatic Akt/PI3K/eNOS and VEGFR-2 pathways.

摘要

背景

肝硬化的特征为肝纤维化和病理性血管生成，导致高动力循环、门体侧支循环形成和异常血管生成。番茄红素主要存在于番茄中，其有益作用包括抗炎、抗氧化、抗纤维化和抗血管生成；然而，尚未研究肝硬化与病理性血管生成之间的关系。本研究旨在探讨番茄红素对胆源性肝硬化大鼠的作用。

方法

评估番茄红素对胆总管结扎（BDL）诱导的胆源性肝硬化大鼠的疗效。假手术大鼠作为手术对照。BDL 或假手术大鼠给予番茄红素（20mg/kg/天，口服灌胃）或载体 4 周后，检测血流动力学、肝功能、门体分流、肝和肠系膜血管生成以及肝血管生成相关蛋白表达。

结果

番茄红素减轻了高动力循环，表现为心脏指数降低和外周血管阻力增加（p<0.05），但对 BDL 大鼠的门静脉压力或肝功能无影响（p>0.05）。番茄红素显著降低了门体侧支循环的分流程度（p=0.04）和肠系膜血管密度（p=0.01），并改善了肝内血管生成和肝纤维化。此外，番茄红素上调了肝内内皮型一氧化氮合酶、蛋白激酶 B（Akt）和磷脂酰肌醇 3-激酶（PI3K），并下调了血管内皮生长因子受体 2（VEGFR-2）蛋白表达（p<0.05）。