首页|大黄素甲醚改善小鼠非酒精性脂肪性肝病的研究

大黄素甲醚改善小鼠非酒精性脂肪性肝病的研究

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大黄素甲醚(physcion,PHY)是一种来源于大黄等中药的蒽醌类化合物。本实验旨在探究PHY对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的改善作用及其机制。采用蛋氨酸胆碱缺乏饲料(methionine-and choline-deficient diet,MCD)喂养6周诱导小鼠NAFLD疾病模型(本实验获得上海中医药大学实验动物伦理委员会批准,批准号:PZSHUTCM190705019)。结果显示,PHY(5和20mg·kg-1)能改善MCD诱导NAFLD小鼠的肝损伤,减轻肝脏脂肪累积,降低升高的NAFLD活动性评分(NAFLD activity score,NAS)。Western blot及酶活力实验结果提示,PHY能提升肝脏及L-02细胞中肉毒碱棕榈酰基转移酶1A(carnitine palmitoyltransferase 1A,CPT1A)蛋白表达及酶活力,但real-time PCR结果显示PHY不影响Cpt1a mRNA表达。免疫荧光结果提示,PHY(10和25 μmol·L-1)能缓解游离脂肪酸(non-esterified fatty acids,NEFA)诱导的人正常肝L-02细胞中的线粒体损伤。Seahorse实验结果提示,PHY给药后能提升L-02细胞内线粒体基础呼吸能力、最大呼吸能力、ATP合成和储备呼吸能力,但不影响线粒体质子漏。以上研究表明,PHY可能通过改善线粒体功能,促进脂肪酸β氧化,减少肝脏中脂肪的堆积,发挥改善NAFLD的药效。
The improvement provided by physcion on non-alcoholic fatty liver disease in mice
Physcion(PHY)is an anthraquinone compound derived from traditional Chinese medicine such as Rhei Radix et Rhizoma.The aim of this study is to investigate the improvement of PHY on non-alcoholic fatty liver disease(NAFLD)and its underlying mechanism.NAFLD was induced in mice by feeding with the methionine-and choline-deficient diet(MCD)for 6 weeks.This experiment was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine(approval number:PZSHUTCM190705019).The results displayed that PHY(5 and 20 mg·kg-1)reversed liver damage,reduced hepatic lipid accumulation and decreased the elevated NAFLD activity score(NAS)in MCD-fed NAFLD mice.Results from Western blot and enzyme activity demonstrated that PHY could enhance the protein expression and enzyme activity of carnitine palmitoyltransferase 1A(CPT1A)in the liver and L-02 cells,but it did not affect Cpt1α mRNA expression.Immunofluorescence results indicated that PHY(10 and 25 μmol·L-1)could reduce the mitochondrial injury induced by non-esterified fatty acids(NEFA)in L-02 cells.Results from seahorse assay showed that PHY could enhance mitochondrial basic respiration,maximal respiration,ATP synthesis and reserve respiration in L-02 cells treated with NEFA,but had no effect on mitochondrial proton leakage.In summary,PHY reversed mitochondrial damage and enhanced fatty acid β-oxidation,thereby reducing hepatic steatosis and improving NAFLD.

physcionnon-alcoholic fatty liver diseasecarnitine palmitoyltransferase 1Aβ-oxidationmitochondrial damage

张进宇、张少波、徐红、欧阳豪、季莉莉

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上海中医药大学中药研究所,中药标准化教育部重点实验室,中药新资源与质量标准综合评价国家中医药管理局重点研究室,上海市复方中药重点实验室,上海 201203

上海中医药大学附属岳阳中西医结合医院肝病科,上海 201203

大黄素甲醚 非酒精性脂肪性肝病 肉毒碱棕榈酰基转移酶1A β氧化 线粒体损伤

国家自然科学基金国家自然科学基金

8227399482173958

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(4)
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