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

作　　者：周红萍 杨兴鑫 庄让笑[3] 邵益丹[3] 席建军[3] 廖莉 任白鹭 王萍萍 余舒莹 史婷婷[3] ZHOU Hongping;YANG Xingxin;ZHUANG Rangxiao;SHAO Yidan;XI Jianjun;LIAO Li;REN Bailu;WANG Pingping;YU Shuying;SHI Tingting(Department of Pharmacy, the Children Hospital of Hangzhou, Hangzhou 310000, Zhefiang, China;College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming 650500, Yunnan, China;the Xixi Hospital of Zhejiang Chinese Medical University, Hangzhou 310023, Zhejiang , China)

机构地区：[1]杭州市儿童医院药剂科,浙江杭州31000 [2]云南中医学院中药学院 [3]浙江中医药大学附属杭州市西溪医院

出　　处：《中国临床药理学与治疗学》2018年第3期263-270,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：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)

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mi RNA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;micro RNA芯片检测肝组织的mi RNA表达谱;荧光定量PCR对mi RNA进行验证;采用荧光定量PCR和Western blot法对目标mi RNA进行靶基因预测并进行验证。结果:根据检测结果,初步确定mi RNA199a-5p和mi RNA-378-5p是NAFLD的关键mi RNA,脂蛋白脂酶(lipoprotein lipase,Lpl)是mi RNA199a-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mi RNA-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。AIM： To primarily investigate the protective effect of active carbon N-acetylcysteine sustained-release microcapsules（ ACNAC） on nonalcoholic fatty liver disease（ NAFLD） in young rats and explore its effect on mi RNA 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 mi RNA expression spectra of liver tissues was detected by micro RNA microarray. The mi RNA was verified by fluorescence quantitative PCR. The target gene prediction and validation were performed for target mi RNA by fluorescence quantitative PCR and Western blot. RESULTS： mi RNA199 a-5 p and mi RNA-378-5 p were the key mi RNA of NAFLD,Lpl was the target gene of mi R199 a-5 p,and srebp1 and C/EBP-αwere the target genes of mi R-378-5 p. 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.

关 键 词：N-乙酰半胱氨酸 非酒精性脂肪肝病 MIRNA LPL Srebp1 C/EBP-α 

分 类 号：R965.2[医药卫生—药理学]