Jobara Kanta, Kaido Toshimi, Hori Tomohide, Iwaisako Keiko, Endo Kosuke, Uchida Yoichiro, Uemoto Shinji
Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nutrition. 2014 Oct;30(10):1195-207. doi: 10.1016/j.nut.2014.02.005. Epub 2014 Feb 28.
Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model.
Progressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model.
Macroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP group's whole liver tissue.
A WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis.
肝纤维化及随后的肝硬化是全球主要的死亡原因，但报道的有效抗纤维化疗法很少。乳清水解肽（WHP）是牛乳的主要肽成分，在实验模型中具有抗炎作用。富含WHP的饮食在临床领域广泛用作免疫调节饮食（IMD）。然而，WHP对肝纤维化的影响仍不清楚。本研究的目的是探讨WHP在大鼠肝硬化模型中的抗纤维化作用。
通过腹腔内重复注射二甲基亚硝胺（DMN）3周诱导进行性肝纤维化。给大鼠喂食富含WHP的IMD（WHP组）或对照肠内饮食（对照组）。比较两组之间的肝纤维化程度。使用从喂食WHP饮食的大鼠分离的肝细胞检查肝细胞保护作用。在DMN肝硬化模型中研究肝组织中的活性氧和谷胱甘肽。
WHP组肝纤维化的宏观和微观进展明显受到抑制。WHP组血清肝酶和透明质酸水平升高以及肝组织羟脯氨酸含量显著降低。从喂食富含WHP的IMD的大鼠中分离出的经DMN攻击后的坏死肝细胞率显著降低。在DMN肝硬化模型中，WHP组全肝组织中的活性氧显著降低，谷胱甘肽显著升高。
富含WHP的IMD通过直接的肝细胞保护作用和通过谷胱甘肽合成的抗氧化作用有效预防了DMN诱导的大鼠肝纤维化进展。
