[1]唐斌林,王亚伟,祥蔚,等.线粒体靶向小分子IR-61改善小鼠非酒精性脂肪肝[J].第三军医大学学报,2018,40(04):296-301.
 TANG Binlin,WANG Yawei,XIANG Wei,et al.Effect of mitochondrial targeting small molecule IR-61 in attenuating non-alcoholic fatty liver in mice[J].J Third Mil Med Univ,2018,40(04):296-301.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第04期
页码:
296-301
栏目:
基础医学
出版日期:
2018-02-28

文章信息/Info

Title:
Effect of mitochondrial targeting small molecule IR-61 in attenuating non-alcoholic fatty liver in mice
作者:
唐斌林王亚伟祥蔚缪洪明史春梦
陆军军医大学(第三军医大学):军事预防医学系全军复合伤研究所,创伤、烧伤与复合伤国家重点实验室,基础医学院生物化学与分子生物学教研室 
Author(s):
TANG Binlin WANG Yawei XIANG Wei MIAO Hongming SHI Chunmeng

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Faculty of Military Preventive Medicine; Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
IR-61非酒精性脂肪肝固醇调节元件结合蛋白1c乙酰辅酶A 羧化酶1 
Keywords:
IR-61 non-alcoholic fatty liver disease sterol regulatory element binding protein 1c acetyl-CoA carboxylase 1
分类号:
R282.71;R575.5;R969
文献标志码:
A
摘要:

目的     探讨线粒体靶向七甲川花菁类荧光小分子IR-61对小鼠非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)模型的治疗效果。方法    通过喂养高脂饲料建立NAFLD小鼠模型,腹腔注射磷酸缓冲盐溶液(phosphate buffer saline,PBS)或IR-61,治疗18周后,取肝脏组织切片HE常规染色,显微镜下观察,采用酶比色法检测肝脏和血清甘油三酯(triglyceride,TG)含量,Real-time PCR和Western blot法检测固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c,SREBP-1c)、乙酰辅酶A羧化酶1(acetyl-CoA carboxylase-1,ACC1)、过氧化物酶体增殖物激活受体α(peroxisome proliferatoractivated receptor-α,PPARα)和肉毒碱棕榈酰转移酶-1(carnitine palmitoyltransferase-1,CPT1)的mRNA及蛋白表达水平。结果     IR-61可降低高脂诱导的小鼠肝脏TG含量增加,抑制SREBP-1c、ACC1过度表达;同时增加肝脏PPARα、CPT1的表达(P<0-.05);IR-61可明显改善小鼠肝脏的脂肪沉积。结论     IR-61通过抑制高脂诱导的脂肪合成代谢过度增强,促进肝脏脂肪酸氧化,减少肝脏甘油三酯沉积,从而改善非酒精性脂肪肝。

Abstract:

Objective    To investigate the therapeutic effect of IR-61, a mitochondrial targeting heptamethine cyanine dye, on non-alcoholic fatty liver disease (NAFLD) in a mouse model. Methods     Mouse model of NAFLD was established by feeding the mice with a high-fat diet. After the modeling, the mice were treated with intraperitoneal injection of PBS or IR-61 (25 μL/g) once a week for 18 consecutive weeks. HE staining was used to observe the pathological changes in liver tissues, and liver and serum levels of triglyceride (TG) were measured using enzyme colorimetry. Real-time PCR and Western blotting were used to detect the expression levels of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase-1 (ACC1), peroxisome proliferator-activated receptor-α (PPARα) and carnitine palmitoyltransterase-1 (CPT1).  Results    IR-61 treatment reduced high-fat feeding-induced elevation of TG level in the liver of the mice and inhibited the high expression of SREBP-1c and ACC1. IR-61 significantly increased the expression of PPARα and CPT1 in the liver (P<0.05) and markedly improved fatty degeneration of the liver in mice after high-fat feeding.  Conclusion    IR-61 inhibits high-fat feeding-induced increase in fat synthesis, enhances liver fatty acid oxidation, and thereby reduces hepatic TG deposition and improves NAFLD in mice.

参考文献/References:

[1]TOWNSEND S A, NEWSOME P N. Review article: new treatments in nonalcoholic fatty liver disease [J]. Aliment Pharmacol Ther, 2017, 46 (5): 494-507. DOI: 10.1111/apt.14210.
[2]GAN L X, XIANG W, XIE B, et al. Molecular mechanisms of fatty liver in obesity [J]. Front Med, 2015, 9 (3): 275-287. DOI: 10.1007/s1168401504102.
[3]房殿亮, 宁波, 沈薇, 等. SCAPSREBP1cACC1在内质网应激状态下肝细胞脂肪变性中的作用[J]. 中国生物制品学杂志, 2013, 26 (10): 1409-1412.
FANG D L, NING B, SHEN W, et al. SCAPSREBP1cACC1 involves in steatosis under endoplasmic reticulum stress in hepatocytes [J]. Chin J Biol, 2013, 26 (10): 1409-1412.
[4]PARK J W, CHOI W G, LEE P J, et al. The novel resveratrol derivative 3,5diethoxy3′,4′dihydroxytransstilbene induces mitochondrial ROSmediated ER stress and cell death in human hepatoma cells in vitro [J]. Acta Pharmacol Sin, 2017, 38 (11): 1486-1500. DOI: 10.1038/aps.2017.106.
[5]HERNNDEZRODAS M C, VALENZUELA R, ECHEVERRA F, et al. Supplementation with docosahexaenoic acid and extra virgin olive oil prevents liver steatosis induced by a highfat diet in mice through PPARα and Nrf2 upregulation with concomitant SREBP1c and NFkB downregulation [J]. Mol Nutr Food Res, 2017, Sep 21. [Epub]. DOI: 10.1002/mnfr.201700479.
[6]LIU Q, PAN R, DING L, et al. Rutin exhibits hepatoprotective effects in a mouse model of nonalcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipidinduced oxidative injuries [J]. Int Immunopharmacol, 2017, 49: 132-141. DOI: 10.1016/j.intimp.2017.05.026.
[7]OJO B, SIMENSON A J, O’HARA C. Wheat germ supplementation alleviates insulin resistance and cardiac mitochondrial dysfunction in an animal model of dietinduced obesity [J]. Br J Nutr, 2017, 118 (4): 241-249. DOI: 10.1017/ S0007114517002082.
[8]SAMUEL V T, SHULMAN G I. Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases [J]. Cell Metab, 2017, pii: S15504131(17)304874. DOI: 10.1016/j.cmet.2017.08.002.
[9]FERRAMOSCA A, DI GIACOMO M, ZARA V. Antioxidant dietary approach in treatment of fatty liver: New insights and updates [J]. World J Gastroenterol, 2017, 23 (23): 4146-4157. DOI: 10.3748/wjg.v23.i23.4146.
[10]WANG X, CHEN Z L, LUO S L, et al. Development of therapeutic smallmolecule fluorophore for cell transplantation [J]. Adv Funct Mater, 2016, 26 (46): 8397-8407. DOI: 10.1002/adfm.201600996.
[11]ENGIN A. Nonalcoholic fatty liver disease [J]. Adv Exp Med Biol, 2017, 960: 443-467. DOI: 10.1007/9783319483825_19.
[12]SHARMA M, MITNALA S, VISHNUBHOTLA R K, et al. The riddle of nonalcoholic fatty liver disease: progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis [J]. J Clin Exp Hepatol, 2015, 5 (2): 147-158. DOI: 10.1016/j.jceh.2015.02.002.
[13]GUEBREEGZIABHER F, ALIX P M, KOPPE L, et al. Ectopic lipid accumulation: a potential cause for metabolic disturbances and a contributor to the alteration of kidney function [J]. Biochimie, 2013, 95 (11): 1971-1979. DOI: 10.1016/ j.biochi.2013.07.017.
[14]TANAKA N, AOYAMA T, KIMURA S, et al. Targeting nuclear receptors for the treatment of fatty liver disease [J]. Pharmacol Ther, 2017, 179: 142-157. DOI: 10.1016/j.pharmthera.2017.05.011.
[15]XU B, SHEN T, CHEN L, et al. The effect of sitagliptin on lipid metabolism of fatty liver mice and related mechanisms [J]. Med Sci Monit, 2017, 23: 1363-1370.
[16]VALTOLINA C, FAVIER R P. Feline hepatic lipidosis [J]. Vet Clin North Am Small Anim Pract, 2017, 47 (3): 683-702. DOI: 10.1016/j.cvsm.2016.11.014.

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更新日期/Last Update: 2018-02-28