N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病miRNA的影响

doi:10.12092/j.issn.1009-2501.2018.03.004

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (3): 263-270.doi: 10.12092/j.issn.1009-2501.2018.03.004

N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病miRNA的影响

周红萍¹，杨兴鑫²，庄让笑³，邵益丹³，席建军³，廖莉¹，任白鹭¹，王萍萍¹，余舒莹¹，史婷婷³

¹杭州市儿童医院药剂科，杭州 31000，浙江； ²云南中医学院中药学院，昆明 650500，云南； ³浙江中医药大学附属杭州市西溪医院，杭州 310023，浙江

收稿日期:2017-11-07 修回日期:2018-02-20 出版日期:2018-03-26 发布日期:2018-03-28
通讯作者: 史婷婷，女，硕士，药师，主要从事肝病药物的研发和基础研究。 Tel: 0571-86481960 E-mail: shiting0626@126.com
作者简介:周红萍，女，本科，主任药师，主要从事肝病药物的研发。 Tel: 0571-85463950 E-mail:zhouhongping1225@sina.com 杨兴鑫，共同第一作者，男，博士，讲师，主要从事中药药效物质基础研究。 Tel: 0871-65933303 E-mail：yxx78945@163.com
基金资助:
国家自然科学基金（81660596）；杭州市科技局（20130633B09，20140633B29，20142013A60，20130633B10）；浙江省公益计划应用研究项目（2017c33233）

Effects of activated carbon N-acetylcysteine sustained-release microcapsule on miRNA of non-alcoholic fatty liver disease in young rats

ZHOU Hongping¹, YANG Xingxin², ZHUANG Rangxiao³, SHAO Yidan ³, XI Jianjun³, LIAO Li ¹, REN Bailu ¹, WANG Pingping ¹, YU Shuying ¹, SHI Tingting ³

¹Department of Pharmacy, the Children Hospital of Hangzhou, Hangzhou 310000, Zhejiang, China; ² College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan, China; ³the Xixi Hospital of Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang, China

Received:2017-11-07 Revised:2018-02-20 Online:2018-03-26 Published:2018-03-28

摘要/Abstract

摘要：

目的: 初步研究N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病的保护作用，并且探讨其对miRNA及相应的靶基因的影响。方法: 采用高脂饲料喂养的方法复制幼鼠非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）模型。HE染色观察幼鼠肝组织脂肪变性程度；microRNA芯片检测肝组织的miRNA表达谱；荧光定量PCR对miRNA进行验证；采用荧光定量PCR和Western blot法对目标miRNA进行靶基因预测并进行验证。结果: 根据检测结果，初步确定miRNA199a-5p和miRNA-378-5p是NAFLD的关键miRNA，脂蛋白脂酶（lipoprotein lipase,Lpl）是miRNA199a-5p的靶基因，固醇调节元件结合蛋白（sterol regulatory element binding proteins-1,Srebp1）、CCAAT增强子结合蛋白α（CCAAT enhancer binding protein alfa,C/EBP-α）是miRNA-378-5p的靶基因。结论: 推测N-乙酰半胱氨酸活性炭缓释微囊可能通过上调Lpl表达水平，下调Srebp1和C/EBP-α表达水平。这些基因与脂肪肝密切相关，可能对幼鼠NAFLD具有保护作用。

关键词: N-乙酰半胱氨酸, 非酒精性脂肪肝病, miRNA, Lpl, Srebp1, C/EBP-α

Abstract:

AIM: To primarily investigate the protective effect of active carbon N-acetylcysteine sustained-release microcapsules (ACNAC) on non-alcoholic fatty liver disease (NAFLD) in young rats and explore its effect on miRNA and corresponding target genes. METHODS: The models of NAFLD in young rats were produced by high-fat diets; the degree of fatty degeneration in the liver tissue of young rats was observed by HE staining; the miRNA expression spectra of liver tissues was detected by microRNA microarray. The miRNA was verified by fluorescence quantitative PCR. The target gene prediction and validation were performed for target miRNA by fluorescence quantitative PCR and Western blot. RESULTS:miRNA199a-5p and miRNA-378-5p were the key miRNA of NAFLD, Lpl was the target gene of miR199a-5p, and srebp1 and C/EBP-α were the target genes of miR-378-5p. CONCLUSION:ACNAC can up regulate the expression of Lpl and down regulate the expressions of srebp1 and C/EBP-α,which are closely associated with fatty liver, so they may have a protective effect on NAFLD in young rats.

Key words: N-acetylcysteine, non-alcoholic fatty liver disease, miRNA, Lpl, Srebp1, C/EBP-α

中图分类号:

R965.2

周红萍，杨兴鑫，庄让笑，邵益丹，席建军，廖莉，任白鹭，王萍萍，余舒莹，史婷婷. N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病miRNA的影响[J]. 中国临床药理学与治疗学, 2018, 23(3): 263-270.

ZHOU Hongping, YANG Xingxin, ZHUANG Rangxiao, SHAO Yidan, XI Jianjun, LIAO Li, REN Bailu, WANG Pingping, YU Shuying, SHI Tingting. Effects of activated carbon N-acetylcysteine sustained-release microcapsule on miRNA of non-alcoholic fatty liver disease in young rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(3): 263-270.

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N-乙酰半胱氨酸活性炭缓释微囊对幼鼠非酒精性脂肪肝病miRNA的影响

Effects of activated carbon N-acetylcysteine sustained-release microcapsule on miRNA of non-alcoholic fatty liver disease in young rats

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