期刊
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
卷 42, 期 2, 页码 118-125出版社
ELSEVIER MASSON, CORPORATION OFFICE
DOI: 10.1016/j.clinre.2017.09.001
关键词
Hepatic cirrhosis; Portal hypertension; Soluble epoxide hydrolase; Epoxyeicosatrienoic acids
资金
- National Natural Science Foundation of China [81370548]
Background/Aims: Fibrosis and increased intrahepatic vascular resistance are the hallmarks of chronic inflammatory disorders of the liver and cirrhosis. Inhibitors of the enzyme soluble epoxide hydrolase reduce fibrosis in several disease models. The present study aimed at investigating the effects of soluble epoxyhydrolase inhibition with t-TUCB in tetrachloride-induced cirrhosis in rats. Methods: The models were established by CCl4 (2 ml/kg) given subcutaneously for 14 weeks. t-TUCB was concomitantly administered from the tenth week of modelling time. After the models were successfully built, the rats were anesthetized with sodium phenobarbital and portal pressure was determined in the groups. After that, the rats were killed and part of liver tissues were taken for histological analysis. In addition, the levels of intrahepatic inflammatory message factors were measured using real-time polymerase chain reaction (PCR) analysis. The remaining liver samples were processed for assessment of oxidative stress. Results: t-TUCB administration significantly attenuated portal pressure relative to CCl4- only rats. This improvement was associated with decreased deposition of collagen in liver, which was supported by reduced mRNA expression of alpha-smooth muscle actin (alpha-SMA), Collagen I, Collagen III, transforming growth factor (Tincreased matrix metalloproteinase-1, -13 (MMP-1, -13) mRNA expression. In addition, t-TUCB decreased the levels of proinflammatory cytokines, including IL-1 beta, IL-6, IL-10, tumor necrosis factor-alpha(TNF-alpha) and NE-kappa B, within cirrhotic hepatic tissue. Meanwhile, oxidative stress was also alleviated following inhibition of sEH in CCl4-induced models, as evidenced by down-regulated levels of malondialdehyde(MDA) and up-regulated levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Conclusion: The soluble epoxyhydrolase inhibitor, t-TUCB alleviates liver fibrosis and portal hypertension through attenuation of inflammatory response and oxidative stress in tetrachloride induced cirrhosis. (C) 2017 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据