鸡骨草总黄酮碳苷对乙硫氨酸导致的小鼠脂肪肝的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (1): 1-7.

• 基础研究 • 下一篇

鸡骨草总黄酮碳苷对乙硫氨酸导致的小鼠脂肪肝的影响

王昀¹, 陈蜜¹, 江振洲^1,2, 汪豪³, 张陆勇^1,4

¹江苏省新药筛选中心,中国药科大学,南京 210009,江苏;
²药物质量与安全预警教育部重点实验室,中国药科大学,南京 210009,江苏;
³中国药科大学天然药物化学教研室,中国药科大学,南京 210009,江苏;
⁴江苏省药效研究与评价服务中心,中国药科大学,南京 210009,江苏

收稿日期:2013-05-16 修回日期:2014-01-08 出版日期:2014-01-27 发布日期:2014-02-12
通讯作者: 张陆勇,男,教授,博士生导师,主要从事分子毒理学和肝脏药理学研究。E-mail: lyzhang@cpu.edu.cn
作者简介:王昀,女,在读博士,主要从事肝脏药理和分子毒理学研究。E-mail: gre0602@163.com
基金资助:
国家“十一五”重大新药创制科技重大专项(2009ZX09103-315);国家“十二五”重大新药创制专项(2013ZX09301-303-003);高等学校学科创新引智计划(111-2-07);2011年度江苏省高等学校优秀科技创新团队(200707008)和国家自然科学基金(81172955)

Protective effect of total Flavonoid C-glycosides from Abrus mollis extract on fatty liver induced by DL-Ethionine in mice

WANG Yun¹, CHEN Mi¹, JIANG Zhen-zhou^1,2, WANG Hao³, ZHANG Lu-yong^1,4

¹Jiangsu Centre for Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
²Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
³Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
⁴Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2013-05-16 Revised:2014-01-08 Online:2014-01-27 Published:2014-02-12

摘要/Abstract

摘要： 目的: 研究鸡骨草总黄酮碳苷(AME)对乙硫氨酸(DL-E)所致小鼠脂肪肝的影响,并探讨其作用机制。方法: ICR小鼠随机分为4组:对照组,DL-E造模组,AME组和AME+DL-E组,每组8只。用AME连续灌胃给予AME组和AME+DL-E组小鼠 7 d,另外两组给予溶剂对照(三蒸水),第7天灌胃给予DL-E组和AME+DL-E组 250 mg/kg DL-E造模,其他两组给予溶剂对照(0.2% CMC-Na)。造模 1 h 后再次灌胃给予所有小鼠AME或溶剂对照(三蒸水),造模 22 h 后收集血样和肝组织,采用生化法测定血清脂质和转氨酶水平,肝脏TG以及TC含量。采用实时定量PCR的方法测定肝脏中相关脂代谢基因水平。结果: AME可以显著减少小鼠肝脏脂肪空泡的数量和脂变的面积,降低TG和TC含量以及血清转氨酶水平。在脂质相关代谢基因的调控上,AME可以下调DL-E导致的固醇调节元件结合蛋白-1(Sterol regulatory element binding protein 1, SREBP-1)、脂肪酸合成酶(Fatty acid synthase, FAS)和乙酰辅酶A羧化酶(Acetyl-CoA carboxylase 1, ACC1)的高表达,并且AME可以逆转DL-E对过氧化物酶体增殖物活化受体α (Peroxisome proliferator activatived receptor α, PPARα)和肉碱棕榈酰转移酶1α (Carnitine palmitoyltransferase 1α, CPT-1α)的抑制作用。结论: AME对DL-E引起的小鼠肝脏脂肪蓄积具有保护作用,并且这种作用主要是通过减少脂质合成,促进脂质氧化代谢来实现的。

关键词: 鸡骨草总黄酮碳苷, 肝损伤, 脂代谢, 固醇调节元件结合蛋白, 脂肪酸合成酶, 过氧化物酶体增殖物活化受体α

Abstract: AIM: To study the effect of total flavonoid C-glycosides from Abrus mollis extract (AME) on lipid dysregulation induced by Ethionine (DL-E).METHODS: ICR mice were randomly assigned to four groups (n=8): Control, DL-E, AME and AME+DL-E groups. Mice were gavaged with AME (200 mg/kg) for 7 days. At day 7, mice of DL-E and AME+DL-E group were gavaged with DL-E (250 mg/kg), other two groups were treated with vehicle control (0.2% CMC-Na). Serum and liver tissues were collected 22 h after administration of DL-E. The contents of hepatic lipids, serum lipids and ALT, AST levels were measured. The expressions of key genes involved in lipid metabolism were also observed by real-time PCR.RESULTS: The results indicated that AME provided significant protection against fatty liver by inhibiting the elevation of serum lipids, serum transaminase, reducing hepatic TG and TC accumulation, ameliorating the severity of pathological changes. Furthermore, AME significantly decreased DL-E-induced SREBP-1, FAS and ACC1 high expressions, which resulting in the lipid homeostasis. The down-regulation of CPT-1α and PPARα that reflect fatty acid metabolism induced by DL-E were reversed by AME treatment.CONCLUSION: The results indicated AME has hepatoprotective effect on Ethionine-induced fatty liver in mice and the effect was mostly due to the regulation on lipid synthesis and fatty acid metabolism.

Key words: Abrus mollis, Liver injury, Lipid metabolism, SREBP, FAS, PPARα

中图分类号:

R965.2

王昀, 陈蜜, 江振洲, 汪豪, 张陆勇. 鸡骨草总黄酮碳苷对乙硫氨酸导致的小鼠脂肪肝的影响[J]. 中国临床药理学与治疗学, 2014, 19(1): 1-7.

WANG Yun, CHEN Mi, JIANG Zhen-zhou, WANG Hao, ZHANG Lu-yong. Protective effect of total Flavonoid C-glycosides from Abrus mollis extract on fatty liver induced by DL-Ethionine in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(1): 1-7.

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鸡骨草总黄酮碳苷对乙硫氨酸导致的小鼠脂肪肝的影响

Protective effect of total Flavonoid C-glycosides from Abrus mollis extract on fatty liver induced by DL-Ethionine in mice

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