Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats

International Journal of Molecular Sciences

Chun-Hsien Yen¹  Fa-Yauh Lee²  Ming-Chih Hou²  Yi-Hsiang Huang²  Chiao-Lin Chuang²  Shao-Jung Hsu²  Chon Kit Pun²  Hui-Chun Huang²  Ching-Chih Chang² 

[1] Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan;

关键词: liver cirrhosis;    portal hypertension;    angiogenesis;    portosystemic collateral shunting;    glycyrrhizin;   

DOI  :  10.3390/ijms22147662

来源: DOAJ

【 摘 要 】

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

【 授权许可】

Unknown