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小柴胡汤可减少杂交石斑鱼(♂鲈形目鮨科石斑鱼×♀鲈形目鮨科石斑鱼)的肝脂肪变性并改善 D-GalN/LPS 诱导的肝损伤。

Xiaochaihu Decoction reduces hepatic steatosis and improves D-GalN/LPS-induced liver injury in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀).

机构信息

Institute of Modern Aquaculture Science and Engineering, Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou, 510631, China.

Institute of Modern Aquaculture Science and Engineering, Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, School of Life Science, South China Normal University, Guangzhou, 510631, China.

出版信息

Fish Shellfish Immunol. 2019 Aug;91:293-305. doi: 10.1016/j.fsi.2019.05.025. Epub 2019 May 15.

DOI:10.1016/j.fsi.2019.05.025
PMID:31100441
Abstract

Excessive lipid accumulation and chemical abuse can induce fatty liver diseases in fish, but the underlying mechanism and therapies are unknown. The present study aims to evaluate the effects of Xiaochaihu Decoction (XCHD) on the growth performance, lipid metabolism and antioxidant function of hybrid grouper in vitro and in vivo, and provide evidence as to whether it can be potentially used as a medicine for liver diseases in aquaculture. In vitro, steatosis model of hybrid grouper primary hepatocytes were incubated for 48 h in control or lipid emulsion (LE)-containing medium with or without 24 h post-treatment with XCHD. XCHD treatment reversed the LE-induced intracellular lipid accumulation, cell viability and hepatocytes morphological structure. In vivo, a total of 300 hybrid grouper with an average initial weight of 25.43 ± 0.18 g were fed diets containing five graded levels of XCHD at 150-1200 mg/kg diet for 8 weeks. After that, a challenge trial was conducted by injection of D-GalN/LPS to induce liver injury. As a result, dietary supplementation with 150-300 mg/kg XCHD diets can significant improve growth performance and feed utilization (P < 0.05). Dietary XCHD down-regulated the expression of lipogenic-related genes (G6PD, DGAT2 and ME1) and up-regulated lipolysis-related genes (ATGL, PPARα and LPL) expression in the liver of hybrid grouper. Livers challenged with D-GalN/LPS exhibited extensive areas of vacuolization with the disappearance of nuclei and the loss of hepatic architecture. These pathological alterations were ameliorated by XCHD treatment. XCHD significantly down-regulated the D-GalN/LPS induced apoptosis-related genes caspase-3, caspase-9 and p53 mRNA expression and up-regulated the antioxidant-related genes CAT and MnSOD mRNA expression in dose dependent manner, respectively. XCHD potently reduced hepatic lipid accumulation and enhanced antioxidant capability in hybrid grouper and may be a potential fish-feed additive to prevent fatty liver diseases onset and progression.

摘要

过量的脂质积累和化学滥用会导致鱼类脂肪肝疾病,但潜在的机制和治疗方法尚不清楚。本研究旨在评估小柴胡汤(XCHD)对体外和体内杂交石斑鱼生长性能、脂质代谢和抗氧化功能的影响,并为其是否可作为水产养殖肝病药物提供依据。在体外,用含或不含脂质乳剂(LE)的培养基孵育杂交石斑鱼原代肝细胞 48 小时,并在 LE 处理后 24 小时用 XCHD 进行后处理。XCHD 处理逆转了 LE 诱导的细胞内脂质积累、细胞活力和肝细胞形态结构。在体内,用含有五个不同浓度 XCHD 的饲料喂养 300 条平均初始体重为 25.43±0.18g 的杂交石斑鱼 8 周。之后,通过注射 D-GalN/LPS 诱导肝损伤进行攻毒试验。结果表明,饲粮添加 150-300mg/kg XCHD 可显著提高生长性能和饲料利用率(P<0.05)。XCHD 下调了杂交石斑鱼肝脏中与脂质生成相关的基因(G6PD、DGAT2 和 ME1)的表达,并上调了与脂肪分解相关的基因(ATGL、PPARα 和 LPL)的表达。用 D-GalN/LPS 处理的肝脏表现出广泛的空泡化区域,细胞核消失,肝组织结构丧失。XCHD 处理改善了这些病理改变。XCHD 显著下调了 D-GalN/LPS 诱导的凋亡相关基因 caspase-3、caspase-9 和 p53 mRNA 的表达,并呈剂量依赖性地上调了抗氧化相关基因 CAT 和 MnSOD mRNA 的表达。XCHD 可有效减少杂交石斑鱼肝脏脂质积累,增强抗氧化能力,可能是预防脂肪肝疾病发生和进展的潜在鱼类饲料添加剂。

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