Abstract

Context

Glucagon-like peptide 1 (GLP-1) and α-tocopheryl quinone can promote the growth of intestinal flora and affect the pathogenesis of non-alcoholic steatohepatitis (NASH).

Objective

This study determines the molecular mechanism of the effect of tocopheryl quinone in the treatment of high cholesterol and cholate diet (HFCC)-induced NASH.

Materials and methods

Thirty-two male Sprague Dawley (SD) rats grouped as lean control (LC), LC + tocopheryl quinone (1 mL of 3 × 10⁶ dpm tocopheryl quinone via i.p. injection), HFCC (5.1 kcal/g of fat diet), and HFCC + tocopheryl quinone. Profiles of intestinal flora were assessed by 16S ribosomal ribonucleic acid–based analysis. Levels and activity of GLP-1, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in intestinal tissues were detected by immunohistochemistry (IHC), Western blot and enzyme-linked immunosorbent assay (ELISA).

Results

HFCC rats presented higher levels of cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), while tocopheryl quinone reversed the effects of HFCC. HFCC dysregulated malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), Vitamin E, 12-hydroxyeicosatetraenoic acid (12-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) and nuclear factor kappa B (NF-κB), and the effects of HFCC were reversed by the treatment of tocopheryl quinone. Also, GLP-1 in the HFCC group was down-regulated while the IL-6 and TNF-α activity and endotoxins were all up-regulated. HFCC significantly decreased the number and diversity of bacteria, whereas tocopheryl quinone substantially restored the balance of intestinal flora and promoted the growth of both Bacteroides and Lactobacilli in vitro.

Discussion and conclusions

α-Tocopheryl quinone relieves HFCC-induced NASH via regulating oxidative stress, GLP-1 expression, intestinal flora imbalance, and the metabolism of glucose and lipids.

中文翻译：

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生育酚醌通过恢复大鼠肠道菌群平衡上调胰高血糖素样肽 1 (GLP-1) 的表达来改善非酒精性脂肪性肝炎 (NASH) 相关的葡萄糖和脂质代谢异常

摘要

语境

胰高血糖素样肽1（GLP-1）和α-生育酚醌可促进肠道菌群的生长，影响非酒精性脂肪性肝炎（NASH）的发病机制。

客观的

本研究确定了生育酚醌治疗高胆固醇和胆酸盐饮食（HFCC）诱导的 NASH 作用的分子机制。

材料和方法

32 只雄性 Sprague Dawley (SD) 大鼠分组为瘦对照 (LC)、LC + 生育酚醌（1 mL 的 3 × 10 ⁶ dpm 生育酚醌，通过ip 注射）、HFCC（5.1 kcal/g 脂肪饮食）和HFCC + 生育酚醌。通过基于 16S 核糖体核糖核酸的分析评估肠道菌群的概况。采用免疫组化（IHC）、Western印迹和酶联免疫吸附试验（ELISA）检测肠组织中GLP-1、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的水平和活性。

结果

HFCC 大鼠表现出更高水平的胆固醇、低密度脂蛋白 (LDL) 和高密度脂蛋白 (HDL)，而生育酚醌则逆转了 HFCC 的作用。HFCC 失调的丙二醛 (MDA)、谷胱甘肽 (GSH)、超氧化物歧化酶 (SOD)、维生素 E、12-羟基二十碳四烯酸 (12-HETE)、13-羟基十八碳二烯酸 (13-HODE) 和核因子 kappa B (NF-κB) ，并且 HFCC 的作用通过生育酚醌的处理被逆转。此外，HFCC 组中的 GLP-1 下调，而 IL-6 和 TNF-α 活性和内毒素均上调。HFCC 显着降低了细菌的数量和多样性，而生育酚醌在体外显着恢复了肠道菌群的平衡并促进了拟杆菌属和乳酸杆菌的生长.

讨论和结论

α-生育酚醌通过调节氧化应激、GLP-1 表达、肠道菌群失衡以及糖脂代谢来缓解 HFCC 诱导的 NASH。