College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China; Department of Medicine, University of Louisville, Louisville, KY, USA.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
J Nutr Biochem. 2018 Aug;58:138-149. doi: 10.1016/j.jnutbio.2018.04.011. Epub 2018 May 1.
Hepatic fibrosis is a common pathological basis of liver cirrhosis and hepatocellular carcinomas. So, prevention and treatment of liver fibrosis is one of the crucial therapeutic goals in hepatology. Organic selenium, glutathione or probiotics supplementation could ameliorate hepatic fibrosis, respectively. The purpose of this study is to develop a novel selenium-glutathione-enriched probiotics (SGP) and to investigate its protective effect on CCl-induced liver fibrosis in rats. Yeast strains with the high-yield glutathione were isolated and identified by analysis of 26S ribosomal DNA sequences. The fermentation parameters of SGP were optimized through single-factor, Plackett-Burman (PB) design and response surface methodology (RSM). The final SGP contained 38.4 μg/g of organic selenium, 34.1 mg/g of intracellular glutathione, approximately 1×10 CFU/g live Saccharomyces cerevisiae and 1×10 CFU/g live Lactobacillus acidophilus. SGP had better protective effects on liver fibrosis than selenium, glutathione or probiotics, respectively. The hepatic silent information regulator 1 (SIRT1) level was down-regulated and oxidative stress, endoplasmic reticulum (ER) stress, inflammation and phosphorylated MAPK was increased in CCl-treated rats. However, SGP can significantly reverse these changes caused by CCl. Our findings suggest that SGP was effective in attenuating liver fibrosis by the activation of SIRT1 signaling and attenuating hepatic oxidative stress, ER stress, inflammation and MAPK signaling.
肝纤维化是肝硬化和肝细胞癌的常见病理基础。因此,预防和治疗肝纤维化是肝病学的重要治疗目标之一。有机硒、谷胱甘肽或益生菌的补充分别可以改善肝纤维化。本研究旨在开发一种新型富硒-谷胱甘肽益生菌(SGP),并研究其对 CCl 诱导的大鼠肝纤维化的保护作用。通过分析 26S 核糖体 DNA 序列,分离并鉴定出产高谷胱甘肽的酵母菌株。通过单因素、Plackett-Burman(PB)设计和响应面法(RSM)优化 SGP 的发酵参数。最终的 SGP 含有 38.4μg/g 的有机硒、34.1mg/g 的细胞内谷胱甘肽、约 1×10 CFU/g 的活酿酒酵母和 1×10 CFU/g 的活嗜酸乳杆菌。SGP 对肝纤维化的保护作用明显优于硒、谷胱甘肽或益生菌。沉默信息调节因子 1(SIRT1)水平在 CCl 处理的大鼠中下调,氧化应激、内质网(ER)应激、炎症和磷酸化 MAPK 增加。然而,SGP 可以显著逆转 CCl 引起的这些变化。我们的研究结果表明,SGP 通过激活 SIRT1 信号通路和减轻肝氧化应激、ER 应激、炎症和 MAPK 信号通路,有效减轻肝纤维化。