药学学报, 2017, 52(1): 106-112
引用本文:
钟丽萍, 李瑾, 王凤忠, 朱海波, 侯旭杰. 虫草素对ob/ob小鼠非酒精性脂肪肝的改善作用及机制研究[J]. 药学学报, 2017, 52(1): 106-112.
ZHONG Li-ping, LI Jin, WANG Feng-zhong, ZHU Hai-bo, HOU Xu-jie. Protective effect and underlying mechanism of cordycepin on non-alcoholic fatty liver in ob/ob mice[J]. Acta Pharmaceutica Sinica, 2017, 52(1): 106-112.

虫草素对ob/ob小鼠非酒精性脂肪肝的改善作用及机制研究
钟丽萍1, 李瑾2, 王凤忠2, 朱海波3, 侯旭杰1
1. 塔里木大学生命科学学院, 南疆特色农产品深加工兵团重点实验室, 新疆 阿拉尔 843300;
2. 中国农业科学院农产品加工研究所, 北京 100193;
3. 天然药物活性物质与功能国家重点实验室, 新药作用机制研究与药效学评价北京重点实验室, 中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
探讨虫草素对ob/ob小鼠非酒精性脂肪肝的改善作用及保护机制。将12周龄的雄性B6.V-Lepob/Lepob小鼠,按照血糖和体重分层后随机分为5组,并以C57BL/6J小鼠为对照组。每周监测一次体重和摄食,在给药2周和4周时,眼眶静脉取血测定血清中的各项生化指标,在给药5周时,进行胰岛素耐量实验,在给药7周后取肝脏组织对甘油三酯、胆固醇及炎症因子含量进行检测,并进行苏木精-伊红染色和油红O染色;提取肝组织的总RNA,采用实时定量PCR技术分析与脂质合成和炎症相关基因的表达。结果显示,虫草素可以有效降低ob/ob小鼠血脂水平,改善肝功能,明显降低肝脏组织脂质含量和炎症因子水平,而对胰岛素抵抗未见改善作用。实时定量PCR结果表明,虫草素可显著降低ob/ob小鼠肝脏组织中与脂质合成及炎症相关mRNA的表达。结果提示,虫草素对ob/ob小鼠非酒精性脂肪肝具有改善作用,其作用机制可能与下调脂质合成和炎症相关基因表达有关。
关键词:    非酒精性脂肪肝      虫草素      ob/ob小鼠      脂质合成      炎症因子     
Protective effect and underlying mechanism of cordycepin on non-alcoholic fatty liver in ob/ob mice
ZHONG Li-ping1, LI Jin2, WANG Feng-zhong2, ZHU Hai-bo3, HOU Xu-jie1
1. Xinjiang Production & Construction Corps Key Laboratory of Deep Processing of Agricultural Products in South Xinjiang, College of Life Science, Tarim University, Alar 843300, China;
2. Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
3. State Key Laboratory for Bioactive Substances and Functions of Natural Medicines;Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
This study is designed to investigate the protective effect and mechanism of cordycepin on nonalcoholic fatty liver in ob/ob mice. Twelve-week-old male ob/ob mice were divided into 5 groups according to their body weight and blood glucose, and C57BL/6J mice were used in the control group. The animals were orally administered with cordycepin for 7 weeks. Body weight and food intake were measured once a week. Blood were collected from ophthalmic venous and biochemical indexes were determined at the 2nd and 4th week. Insulin tolerance test was performed at the 5th week. After 7 weeks of administration, liver tissues were collected to determine the contents of triglycerides and total cholesterol, and pro-inflammatory cytokines. Liver histology was performed by hematoxylin-eosin and oil-red O staining. Total RNA were extracted from liver tissues and the levels of lipid metabolism-related and inflammation-related genes were detected by real time PCR. Cordycepin effectively reduced the blood lipids level and improved liver function. Nevertheless, it did not improve insulin resistance in ob/ob mice. Cordycepin significantly reduced the contents of triglycerides and cholesterol, and the levels of pro-inflammatory cytokines in liver tissues. Moreover, cordycepin remarkably suppressed the expression of genes related to lipids synthesis and inflammation. These results indicate that cordycepin may improve non-alcoholic fatty liver in ob/ob mice, and the underlying mechanism may be associated with decreased expression of genes related to lipids synthesis and inflammation.
Key words:    non-alcoholic fatty liver disease    cordycepin    ob/ob mice    lipids synthesis    inflammatory cytokines   
收稿日期: 2016-09-07
DOI: 10.16438/j.0513-4870.2016-0886
基金项目: 国家自然科学基金(81273514,91539126);中国农业科学院科技创新工程(125161015000150013).
通讯作者: 朱海波,Tel:86-997-4681613,E-mail:houxujie@sina.com
Email: houxujie@sina.com
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