酮替芬对高糖高脂饮食大鼠胰岛素抵抗的干预研究

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (7): 761-765.

酮替芬对高糖高脂饮食大鼠胰岛素抵抗的干预研究

邹柳义, 王美荣, 倪连松

温州医学院附属第一医院内分泌科,温州 325000,浙江

收稿日期:2013-07-06 修回日期:2014-06-16 发布日期:2014-07-21
通讯作者: 倪连松,男,主任医师,硕士生导师,研究方向:糖尿病肾病发病机理及治疗。 Tel: 13758876020 　E?mail: nils1014@163.com
作者简介:邹柳义,男,研究生,研究方向:糖尿病肾病发病机理及治疗。 Tel: 18066445996 E-mail: zouliuyi198713@163.com

Effects of ketotifen on insulin resistance in high-carbon hydrate-fat diet rats

ZOU Liu-yi, WANG Mei-rong, NI Lian-song

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

Received:2013-07-06 Revised:2014-06-16 Published:2014-07-21

摘要/Abstract

摘要： 目的观察酮替芬(ketotifen,Ket)对高糖高脂饮食大鼠胰岛素抵抗的干预作用。方法将30只雄性SD大鼠随机分为3组,即A组:正常饮食+生理盐水,B组:高糖高脂+生理盐水,C组:高糖高脂+生理盐水+酮替芬。实验完毕后,分别测量各组大鼠体质量,检测各组大鼠空腹血糖、血清胰岛素水平,血清、肝组织IL-6、TNF-α水平,检测各组大鼠相同部位肝组织糖原含量。结果 (1)胰岛素抵抗指数A组(-3.23±0.31)与B组(-3.99±0.20)相比,P<0.01;B组(-3.99±0.20)与C组(-3.66±0.18)相比,P<0.01。体质量B组(588.53±27.91) g 与C组(522.52±30.14) g 相比,P<0.01。肝组织糖原含量B组(6.18±1.42) mg/g 与C组(7.89±1.64) mg/g 相比,P<0.01。(2)血清IL-6水平B组(47.07±10.37) pg/mL 与C组(36.48±7.89) pg/mL 相比,P<0.01。血清TNF-α水平B组(16.54±2.54) pg/mL 与C组(12.63±2.19) pg/mL 相比,P<0.01。肝组织IL-6水平B组(2 152.34±262.16) pg/mL 与C组(1 726.91±192.63) pg/mL 相比,P<0.01。肝组织INF-α水平B组(1 275.50±337.50) pg/mL 与C组(1 013.25±171.92) pg/mL 相比,P<0.01。肝组织糖原含量B组(6.18±1.42) mg/g 与C组(7.89±1.64) mg/g 相比,P<0.01。结论酮替芬可以改善高糖高脂饮食大鼠机体及肝组织的胰岛素抵抗,降低高糖高脂饮食大鼠体质量。肥大细胞膜稳定剂酮替芬可能通过稳定肥大细胞膜抑制肥大细胞活化,减轻机体炎症反应,从而改善高糖高脂饮食诱导的大鼠胰岛素抵抗。

关键词: 酮替芬, 肥大细胞, 胰岛素抵抗, 白介素-6, 肿瘤坏死因子-α

Abstract: AIM: To investigate the effects of ketotifen on insulin resistance in high-carbon hydrate-fat diet wistar rats. METHODS: Male SD rats were randomly divided into three groups: group A (basal diet), group B (high-carbon hydrate-fat diet), group C (high-carbon hydrate-fat diet and ketotifen). And then the body weights, fasting blood glucose (FBG), fasting insulin (FINS) , riglyceride (TG) and low density lipoprotein cholesterin (LDL-C), interleukin-6 (IL-6) and tumor nectosis factor-α (TNF-α) in serum and liver were measured. RESULTS:Compared with group A, the body weights, FBG and FINS of group B significantly were increased (P<0.05). Compared with group B, the insulin sensitivity index (ISI) and hepatic glycogen levels of group C significantly were increased (P<0.05), the body weights, FBG, FINS, TG and LDL-C levels, IL-6 and TNF-α levels in serum and liver were reduced (P<0.05). CONCLUSION: Ketotifen can ameliorate insulin resistance in high-carbon hydrate-fat diet wistar rats by reducing the body inflammatory reaction.

Key words: ketotifen, mast cell, insulin resistance, IL-6, TNF-α

中图分类号:

R965.2

邹柳义, 王美荣, 倪连松. 酮替芬对高糖高脂饮食大鼠胰岛素抵抗的干预研究[J]. 中国临床药理学与治疗学, 2014, 19(7): 761-765.

ZOU Liu-yi, WANG Mei-rong, NI Lian-song. Effects of ketotifen on insulin resistance in high-carbon hydrate-fat diet rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(7): 761-765.

参考文献

[1] Wellen KE,Hotamisligil GS.Inflammation,stress and diabetes[J]. J Clin Invest, 2005, 115(5): 1111-1119.
[2] Lundequist A, Pejler G.Biological implications of preformed mast cell mediators[J]. Cell Mol Life Sci, 2011, 68(6): 965-975.
[3] Wang J, Shi GP.Mast cell stabilization: novel medication for obesity and diabetes[J]. Diabetes Metab Res Rev, 2011, 27(8): 919-924.
[4] 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 Recepto[J]. Int Arch Allergy Immunol, 2004, 135(4): 313-318.
[5] Galli SJ, Tsai M.IgE and mast cells in allergic disease[J]. Nat Med, 2012, 18(5): 693-704.
[6] Zhang J, Shi GP.Mast cells and metabolic syndrome[J]. Biochim Biophys Acta, 2012, 1822(1): 14-20.
[7] Sun J, Sukhova GK, Wolters PJ, et al.Mast cells promote atherosclerosis by releasing proinflammatory cytokines[J]. Nat Med, 2007, 13(6): 719-724.
[8] Wang Z, Zhang H, Shen XH, et al.Immunoglobulin E and mast cell proteases are potential risk factors of human pre-diabetes and diabetes mellitus[J]. PLoS One, 2011, 6(12): e28962.
[9] Divoux A, Moutel S, Poitou C, et al.Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes[J]. J Clin Endocrinol Metab, 2012, 97(9): E1677-E1685.
[10] 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.
[11] Clore JN, Stillman J, Sugerman H.Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes[J]. Diabetes, 2000, 49(6): 969-974.
[12] Fernandez-Real JM, Vayreda M, Richart C, et al.Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women[J]. J Clin Endocrinol Metab, 2001, 86(3): 1154-1159.
[13] Bastard JP, Maachi M, Van Nhieu JT, et al.Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro[J]. J Clin Endocrinol Metab, 2002, 87(5): 2084-2049.
[14] Plomgaard P, Nielsen AR, Fischer CP, et al.Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes[J]. Diabetologia, 2007, 50(12): 2562-2571.

[1]	全海燕, 江兴, 何璐. 线粒体自噬在肝胰岛素抵抗中作用机制的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(2): 198-204.
[2]	蔡江怡，刘耀，李嘉诚. 膀胱灌注透明质酸钠治疗间质性膀胱炎的温度选择[J]. 中国临床药理学与治疗学, 2020, 25(4): 447-454.
[3]	虞姣姣，杨洋，刘莹，郭晓汐，徐天瑞，安输. 芍药苷通过PI3K/AKT/m-TOR信号途径抑制肥大细胞活化脱颗粒[J]. 中国临床药理学与治疗学, 2019, 24(9): 961-968.
[4]	全海燕，刘玉环，杨丽，阳芳，秦旭平. CGRP通过激活cAMP/PPARγ/eNOS途径改善血管内皮细胞胰岛素抵抗[J]. 中国临床药理学与治疗学, 2019, 24(6): 615-622.
[5]	丁凡，李文雄，张佳莉，张岩. 糖尿病性肌少症发病机制和治疗靶点的研究进展[J]. 中国临床药理学与治疗学, 2019, 24(12): 1428-1433.
[6]	郑丽，莫娟芬，吴加元，郭丽，鲍轶. 基于网络药理学的虎杖抗高血脂作用及信号通路研究[J]. 中国临床药理学与治疗学, 2019, 24(10): 1107-1119.
[7]	汪静，周海斌，顾伟刚，王霞，杨建锋. 酮替芬对腹泻型肠易激综合征患者胃肠道症状、内脏敏感性及肠道肥大细胞的影响[J]. 中国临床药理学与治疗学, 2019, 24(1): 63-70.
[8]	宋美情. 二甲双胍对2型糖尿病伴高血压患者骨密度及胰岛素抵抗、细胞因子的影响[J]. 中国临床药理学与治疗学, 2017, 22(6): 694-698.
[9]	黄巧文，蔡丽生. 右美托咪定对全麻下老年患者腹腔镜结直肠癌手术的应激水平和术后细胞因子影响[J]. 中国临床药理学与治疗学, 2016, 21(7): 802-805.
[10]	张固琴, 杨炯. 罗格列酮对人肥大细胞株HMC-1细胞迁移的影响及机制研究[J]. 中国临床药理学与治疗学, 2015, 20(9): 981-984.
[11]	刘晓颖, 蔡诗婷, 杨敏, 萧定璋, 谭红红, 陈景, 陈少贤, 陈红梅, 杨慧, 余细勇. TLR2/NLRC5参与棕榈酸诱导的心肌细胞凋亡及相关机制研究[J]. 中国临床药理学与治疗学, 2015, 20(7): 763-768.
[12]	沈纪中, 柳航. 高糖饮水诱导代谢综合征小鼠模型的实验研究[J]. 中国临床药理学与治疗学, 2014, 19(9): 1011-1015.
[13]	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.
[14]	陈咨苗, 陈肖俊, 王美荣, 潘亮亮, 胡万里, 倪连松. 酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响[J]. 中国临床药理学与治疗学, 2013, 18(6): 627-632.
[15]	蒋励, 贺碧霞, 丁启龙. 甲状腺激素和肝脏胰岛素抵抗的研究进展[J]. 中国临床药理学与治疗学, 2013, 18(3): 356-360.