酮替芬对高糖高脂饮食诱导肥胖模型大鼠的减肥作用

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (1): 23-28.

酮替芬对高糖高脂饮食诱导肥胖模型大鼠的减肥作用

陈咨苗, 王美荣, 叶婷婷, 顾雪疆, 陈雄, 朱虹, 倪连松

温州医科大学附属第一医院内分泌科,温州 325000,浙江

收稿日期:2013-03-11 修回日期:2013-05-31 出版日期:2014-01-27 发布日期:2014-02-12
作者简介:陈咨苗,男,硕士,主治医师,主要从事糖尿病与胰岛素抵抗发病机制及治疗研究。Tel: 13506528878 E-mail: zimiaochen@163.com
基金资助:
浙江省自然科学基金(LQ12H07003);温州市科技局基金资助(Y20100063)

Antiobesity effect of ketotifen in high-carbon hydrate-fat diet induced obese rats

CHEN Zi-miao,WANG Mei-rong,YE Ting-ting,GU Xue-jiang CHEN Xiong, ZHU Hong, NI Lian-song

Department of Endocrinology,the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000,Zhejiang,China

Received:2013-03-11 Revised:2013-05-31 Online:2014-01-27 Published:2014-02-12

摘要/Abstract

摘要： 目的: 探讨酮替芬对高糖高脂饮食诱导的大鼠肥胖模型的减肥作用及其机制。方法: SD大鼠随机分成肥胖模型组、酮替芬干预组和正常对照组,肥胖模型组和酮替芬干预组以高糖高脂饲料饲喂,正常对照组以基础饲料饲喂,酮替芬干预组每天灌胃给予酮替芬 0.09 mg/kg,持续12周。称重,计算Lee's指数,检测空腹血糖(FBG)、空腹胰岛素(FINS)、瘦素(LEP)、游离脂肪酸(FFA)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α);检测白色脂肪解偶联蛋白2(UCP2)mRNA的表达。结果: 酮替芬明显降低肥胖模型大鼠的体质量及Lee's指数(P<0.05),降低FBG、FINS和LEP水平(P<0.05),降低FFA、TG和LDL-C水平(P<0.05)和IL-6、TNF-α水平(P<0.05),而增加UCP2 mRNA的表达水平(P<0.05)。结论: 酮替芬能够降低肥胖模型大鼠炎症介质和游离脂肪酸水平,减轻高胰岛素血症和高瘦素血症,促进脂肪组织能量代谢,实现减肥作用。

关键词: 酮替芬, 肥胖, 肥大细胞, 炎症, 解偶联蛋白2

Abstract: AIM: To investigate the antiobesity effect and mechanism of ketotifen in high-carbon hydrate-fat diet induced obese rats.METHODS: Male SD rats were randomly divided into three groups:obese group,ketotifen group and normal control group.Rats of obese group and ketotifen group were fed with high-carbon hydrate-fat diet,while the rats of normal control group were fed with basal feed. Rats of ketotifen group were daily given a gavage of ketotifen 0.09 mg/kg for 12 weeks.The body weights were tested and then the Lee's indexes were calculated,The fasting blood glucose(FBG),fasting insulin(FINS) and leptin(LEP), free fatty acid(FFA),riglyceride(TG) and low density lipoprotein cholesterin(LDL-C), interleukin -6(IL-6) and tumor nectosis factor-alpha(TNF-α) were analyzed,UCP2 mRNA in white adipose were measured.RESULTS: Ketotifen reduced body weight and Lee's indexes obviously in obese rats(P<0.05), lowered FBG,FINS and LEP levels and reduced FFA,TG and LDL-C levels significantly(P<0.05).Furthermore,ketotifen could decrease IL-6 and TNF-α levels and increase the UCP2 mRNA expression obviously(P<0.05).CONCLUSION: Ketotifen has antiobesity effects on high-carbon hydrate-fat diet induced obese rats by reduction of inflammation medium and free fatty acid leves,alleviation of hyperinsulinemia and hyperleptindemia and promotion of adipose tissue energy metabolism.

Key words: Ketotifen, Obesity, Mast cell, Inflammation, UCP2

中图分类号:

陈咨苗, 王美荣, 叶婷婷, 顾雪疆, 陈雄, 朱虹, 倪连松. 酮替芬对高糖高脂饮食诱导肥胖模型大鼠的减肥作用[J]. 中国临床药理学与治疗学, 2014, 19(1): 23-28.

CHEN Zi-miao,WANG Mei-rong,YE Ting-ting,GU Xue-jiang CHEN Xiong, ZHU Hong, NI Lian-song. Antiobesity effect of ketotifen in high-carbon hydrate-fat diet induced obese rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(1): 23-28.

参考文献

[1] Wu RL,Anthes JC,Kreutner W,et al.Desloratadine inhibits constitutive and histamine-stimulated nuclear factor- kappaB activity consistent with inverse agonism at the histamine H1 Receptor[J].Int Arch Allergy Immunol,2004,135(4):313-318.
[2] Marshall JS . Mast-cell responses to pathogens[J]. Nat Rev Immunol, 2004, 4(10): 787-799.
[3] Xu JM,Shi GP. Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases[J]. Endocr Rev, 2012,33(1):71-108 .
[4] Zhang J,Shi GP.Mast cells and metabolic syndrome[J].Biochim Biophys Acta,2012,1822(1) :14-20.
[5] Bot I,Biessen EA.Mast cells in atherosclerosis[J].Thromb Haemost,2011, 106 (5) : 820-826.
[6] Liu J,Divoux A,Sun J, et al.Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice[J].Nat Med,2009,15(8): 940-945.
[7] Theoharides TC,Kempuraj D,Tagen M,et al.Differential release of mast cell mediators and the pathogenesis of inflammation[J].Immunol Rev, 2007,217:65-78.
[8] Azadi L,Abbasi H,Deemeh MR,et al.Zaditen(Ketotifen),as mast cell blocker,improves sperm quality,chromatin integrity and pregnancy rate after varicocelectomy[J].Int J Androl,2011,34 (5):446-452.
[9] O'Sullivan M.Therapeutic potential of ketotifen in irritable bowel syndrome (IBS) may involve changes in mast cells at sites beyond the rectum [J].Gut, 2011,60(3):423.
[10] Monument MJ,Hart DA,Befus AD,et al.The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures [J]. Inflamm Res, 2012, 61(4):285-292.
[11] Xing XH, Chen L, Song HX.The preventive effect of anti-asthma particles on inflammatory airway damage of model rats with asthma in remission stage[J].Chin Pediatr Integr Tradit West Med, 2010,2(1):49-51.
[12] 巫冠中, 郭永起, 苏欣,等.大豆黄素衍生物LRXH609的减肥作用及机理探讨[J].中国临床药理学与治疗学,2009,14(5):519-523.
[13] Qiang GF, Feng P, Cui JQ,et al. Effect of leptin and fatty acids on uncoupling protein-2 mRNA in rat islet cells[J].Chin J Endocrinol Metab,2004,20(4):367-368.
[14] Kalupahana NS,Moustaid-Moussa N,Claycombe KJ.Immunity as a link between obesity and insulin resistance[J]. Mol Aspects Med,2012,33(1) :26-34.
[15] Luciani A,Dechoux S,Deveaux V, et al. Adipose tissue macrophages: Mr tracking to monitor obesity-associated inflammation[J]. Radiology,2012, 263(3) :786-793.
[16] Chawla A,Nguyen KD,Goh YP.Macrophage-mediated inflammation in metabolic disease[J]. Nat Rev Immunol,2011,11(11):738-749.
[17] Weisberg SP,Hunter D,Huber R,et al.CCR2 modulates inflammatory and metabolic effects of high-fat feeding[J].J Clin Invest,2006,116(1):115-124.
[18] Kouidhi S,Jarboui S,Clerget Froidevaux MS,et al. Relationship between subcutaneous adipose tissue expression of leptin and obesity in Tunisian patients[J]. Tunis Med,2010,88(8):569-572.
[19] Jung CH,Rhee EJ,Choi JH,et al. The relationship of adiponectin/ leptin ratio with homeostasis model assessment insulin resistance index and metabolic syndrome in apparently healthy korean male adults[J]. Korean Diabetes J,2010,34(4):237-243.
[20] Nau GJ,Richmond JF,Schlesinger A, et al.Human macrophage activation programs induced by bacterial pathogens[J]. Proc Natl Acad Sci USA,2002,99( 3):1503-1508.
[21] Diano S,Horvath TL.Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism[J]. Trends Mol Med,2012,18(1):52-58.
[22] Jia JJ,Zhang X,Ge CR, et al.The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes[J].Obes Rev,2009,10 (5):519-526.
[23] Premaratna SD,Manickam E,Begg DP,et al. Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice[J].Int J Obes (Lond),2012, 36(2) :233-243.
[24] Yonezawa T,Kurata R,Hosomichi K, et al.Nutritional and hormonal regulation of uncoupling protein 2[J].IUBM B Life,2009,61(12): 1123-1131.
[25] Fukuda H,Hirakawa T,Iritani N.Nutritional and hormonal regulation of uncoupling protein gene expression in rat adipocytes[J].J Nutr Sci Vitaminol (Tokyo),2007, 53(5) :426-431.
[26] Scarpace PJ,Nicolson M,Matheny M.UCP2, UCP3 and leptin gene expression: modulation by food restriction and leptin[J].J Endocrinol,1998, 159(2): 349- 357.