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五酯胶囊(五味子提取物)可减轻非酒精性脂肪性肝病发展过程中的肝脂肪变性和炎症。

Wuzhi capsule (Schisandra Sphenanthera extract) attenuates liver steatosis and inflammation during non-alcoholic fatty liver disease development.

机构信息

Department of Organ Transplantation, ChangZheng Hospital, Second Military Medical University, Shanghai, 200003, China.

Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

出版信息

Biomed Pharmacother. 2019 Feb;110:285-293. doi: 10.1016/j.biopha.2018.11.069. Epub 2018 Dec 3.

DOI:10.1016/j.biopha.2018.11.069
PMID:30522014
Abstract

OBJECTIVE

Wuzhi (WZ) capsule contains an ethanol extract of Schisandra sphenanthera. The efficacy of WZ in treating non-alcoholic fatty liver disease (NAFLD) has not yet been elucidated. The present study assessed the effects of WZ on NAFLD.

MATERIAL AND METHODS

A C57BL/6 male mouse model of NAFLD was established by feeding the animals a methionine-choline-deficient (MCD) diet. Mice fed the basal diet were used as controls. Both groups were randomly administered WZ or vehicle by gavage for 5 weeks. Body weight change, liver/body weight ratio, metabolic parameters, and histological changes were assessed. Serum levels of IL-1β, IL-6, IL-10, and TNF-α were analysed by ELISA; mRNA expression of these genes in the liver was studied by real-time PCR. Western blotting was used to analyse the protein levels of PPAR-α, PPAR-γ, MCAD, LCAD, and p65 in the liver.

RESULTS

After 5 weeks of the MCD diet, the liver/body weight ratio of WZ mice was higher than that of control mice. Liver histology revealed significantly less steatosis, inflammation, and necrosis, which was confirmed by decreased intrahepatic triglycerides and serum ALT in WZ-treated mice. WZ also reduced the liver mRNA expression of IL-1β, IL-6, and TNF-α and the serum levels of IL-1β and IL-6. Sensitivity to steatohepatitis due to WZ administration correlated significantly with alterations in the expression of PPAR-α/γ, as well as the NF-κB signalling pathway.

CONCLUSIONS

WZ plays a protective role against MCD-induced steatohepatitis. The underlying mechanism likely involves the upregulation of PPAR-α/γ and downregulation of the NF-κB signalling pathway. Based on its beneficial effects on the liver, WZ is a promising therapeutic for NAFLD patients.

摘要

目的

五味(WZ)胶囊含有五味子的乙醇提取物。WZ 治疗非酒精性脂肪性肝病(NAFLD)的疗效尚未阐明。本研究评估了 WZ 对 NAFLD 的影响。

材料和方法

通过用蛋氨酸-胆碱缺乏(MCD)饮食喂养动物,建立 C57BL/6 雄性小鼠 NAFLD 模型。用基础饮食喂养的小鼠作为对照。两组均通过灌胃随机给予 WZ 或载体 5 周。评估体重变化、肝/体重比、代谢参数和组织学变化。通过 ELISA 分析血清中 IL-1β、IL-6、IL-10 和 TNF-α的水平;通过实时 PCR 研究这些基因在肝脏中的 mRNA 表达。Western 印迹用于分析肝脏中 PPAR-α、PPAR-γ、MCAD、LCAD 和 p65 的蛋白水平。

结果

在 MCD 饮食 5 周后,WZ 小鼠的肝/体重比高于对照组。肝组织学显示脂肪变性、炎症和坏死明显减少,这一点通过 WZ 治疗小鼠肝内甘油三酯和血清 ALT 的减少得到证实。WZ 还降低了肝脏中 IL-1β、IL-6 和 TNF-α 的 mRNA 表达以及血清中 IL-1β 和 IL-6 的水平。WZ 给药对肝炎敏感性的改变与 PPAR-α/γ 以及 NF-κB 信号通路的改变显著相关。

结论

WZ 对 MCD 诱导的脂肪性肝炎具有保护作用。其潜在机制可能涉及 PPAR-α/γ 的上调和 NF-κB 信号通路的下调。基于其对肝脏的有益作用,WZ 是治疗 NAFLD 患者的有前途的药物。

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