蒺藜提取物治疗2型糖尿病药效及其机制研究

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (9): 1006-1010.

蒺藜提取物治疗2型糖尿病药效及其机制研究

赵保胜¹, 李朋收^{2, 3, 4}, 张舒媛⁵, 李春娜^{2, 3, 4}, 刘洋洋^{2, 3, 4}, 时晓娟^{2, 3, 4}, 徐暾海^{2, 3, 4}, 刘铜华^{3, 4}

¹ 北京中医药大学科研实验中心,
² 中药学院,
³ 中医养生学教育部重点实验室,
⁴ 中医养生学北京市重点实验室, 5 管理学院,北京 100029

收稿日期:2013-12-10 修回日期:2014-07-14 出版日期:2014-09-26 发布日期:2014-09-26
通讯作者: 徐暾海,男,教授,研究方向:中药活性成分及质量控制研究。 E-mail: thxu@yahoo.com
作者简介:赵保胜,男,博士,副研究员,研究方向:中药药效与物质基础研究。 Tel: 010-64286291 E-mail: zhaobs1973@163.com
基金资助:
国家自然科学基金面上项目(81374027); 国际科技合作计划(2010DFB33260); 北京中医药大学创新团队项目(2011-CXTD-19); 北京中医药大学中青年教师资助项目(2013-JYBZZ-JS-131)

The efficacy of Fructus Tribuli extract JL201 on type 2 diabetes and its potential mechanisms

ZHAO Bao-sheng¹, LI Peng-shou^{2, 3, 4}, ZHANG Shu-yuan⁵, LI Chun-na^{2, 3, 4}, LIU Yang-yang^{2, 3, 4}, SHI Xiao-juan^{2, 3, 4}, XU Tun-hai^{2, 3, 4}, LIU Tong-hua^{3, 4}

¹ Center of Scientific Experiment;
² School of Chinese Materia Medica;
³ Key Laboratory of Ministry of Education for Health Science of Traditional Chinese Medicine;
⁴ Key Laboratory of Beijing for Health Science of Traditional Chinese Medicine;
⁵ School of management, Beijing University of Chinese Medicine, Beijing 100029, China

Received:2013-12-10 Revised:2014-07-14 Online:2014-09-26 Published:2014-09-26

摘要/Abstract

摘要： 目的观察蒺藜提取物(NO. JL201)对自发性2型糖尿病模型KK^Ay小鼠空腹血糖(FPG)、血胰岛素(Ins)、TNF-α、IFN-β含量及其胰岛细胞TLR3、TLR4 mRNA含量的影响,初步探讨其可能降糖机制。方法 KK^Ay小鼠随机分为模型组、JL201大(20 mg/kg BW)、中(10 mg/kg BW)、小 (5 mg/kg BW) 剂量组和阳性药二甲双胍组(400 mg/kg BW)。每周测定体质量,食、水量和FPG。给药4周后取血,测定小鼠FPG和Ins,计算小鼠Ins敏感性,Real time-PCR法测定胰岛细胞TLR2、TLR4 mRNA含量。结果 JL201不同剂量不同程度地减少了小鼠的进食、饮水量,明显降低KK^Ay小鼠的FPG(P<0.05 或P<0.01)、降低血清Ins含量(P<0.05 或P<0.01),明显升高KK^Ay小鼠胰岛素敏感性(P<0.05),减少TNF-α、IFN-β的血中分泌量。JL201同时可降低胰岛细胞TLR2、TLR4 mRNA含量。结论 JL201有较好的降血糖、增强胰岛素敏感性等作用,并能明显改善多饮、多食的临床症状,其作用可能与降低胰岛细胞TLR2、TLR4 mRNA含量、抑制炎症有关。

关键词: 蒺藜, 2型糖尿病, 药效, 机制研究

Abstract: AIM: To observe the effect of Fructus Tribuli extract (NO. JL201) on the concentration of fasting plasma glucose, blood insulin, TNF-α, IFN-β and that of TLR3, TLR4 mRNA in islet cell on spontaneous type 2 diabetes KK^Ay mice, and explore its potential hypoglycemic mechanisms. METHODS: Mice were randomly allocated into 5 groups: control group, JL201 high -dosage group (20 mg/kg BW), JL201 middle -dosage group (10 mg/kg BW), JL201 low-dosage group (5 mg/kg BW), and positive drug metformin group (400 mg/kg BW). Body weights, food and water intake and fasting plasma glucose (FPG) were measured weekly. Mice were sacrificed after 4 weeks administration to obtain the blood sample and measured the concentration of FPG and insulin (Ins), and calculated the sensitivity of Ins in mice. The concentrations of TLR2, TLR4 mRNA in Islet cell were measured using realtime-PCR method.RESULTS: Different concentration of JL201 reduced the intake of food and water respectively. In addition, the concentration of FPG decreased significantly (P<0.05 or P<0.01) and the concentration of serum Ins also lowed (P<0.05 or P<0.01). However, the sensitivity of Ins increased significantly (P<0.05) and the secretion of TNF-α, IFN-β reduced. At the same time, JL201 could decrease the concentration of TLR2, TLR4 mRNA spontaneously. CONCLUSION: JL201 has beneficial effects on hypoglycemic and strengthening the sensitivity of Ins. Besides, it also can improve polydipsia and polyphagia clinical symptoms. The potential beneficial effects may be associated with decreasing islet cell TLR2, TLR4 mRNA levels and inhibiting inflammation.

Key words: Fructus Tribuli, type 2 diebetes, efficacy, mechanism

中图分类号:

R965.2

赵保胜, 李朋收, 张舒媛, 李春娜, 刘洋洋, 时晓娟, 徐暾海, 刘铜华. 蒺藜提取物治疗2型糖尿病药效及其机制研究[J]. 中国临床药理学与治疗学, 2014, 19(9): 1006-1010.

ZHAO Bao-sheng, LI Peng-shou, ZHANG Shu-yuan, LI Chun-na, LIU Yang-yang, SHI Xiao-juan, XU Tun-hai, LIU Tong-hua. The efficacy of Fructus Tribuli extract JL201 on type 2 diabetes and its potential mechanisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(9): 1006-1010.

参考文献 18

[1]	Hotamisligil GS.Inflammation and metabolic disorders[J]. Nature, 2006, 444(7121): 860-867.
[2]	Poggi M, BasteIica D, GuaI P, et a1. C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet[J]. Diabetologia, 2007, 50(6): 1267-1276.
[3]	侯俊英, 王秀华, 李红, 等. 蒺藜皂苷对缺血再灌注损伤心肌细胞的保护作用[J]. 中国药理学通报, 2004, 20(4):418-420.
[4]	关欣, 纪影实, 李红, 等. 蒺藜皂苷对脑缺血再灌注损伤大鼠的保护作用[J]. 中草药, 2006, 37(6): 904-906.
[5]	石昌杰, 瞿伟菁, 王捷思, 等. 蒺藜皂苷对大鼠动脉粥样硬化形成的影响[J]. 天然产物研究与开发, 2009, 21:53-57, 72.
[6]	李红, 王秀华, 崔佳乐. 注射用蒺藜皂苷的抗血栓形成作用[J]. 吉林大学学报:医学版, 2005, 31(1):14-16.
[7]	张季, 张丹参, 严春临, 等. 蒺藜皂苷对小鼠记忆障碍的影响[J]. 中药药理与临床, 2007,23(3):47-49.
[8]	李明娟, 瞿伟菁, 褚书地, 等. 蒺藜水煎液对小鼠糖代谢中糖异生的作用[J]. 中药材, 2001, 24(8):586-588.
[9]	李明娟, 瞿伟菁, 王熠非, 等. 蒺藜皂苷的降血糖作用[J]. 中药材, 2002, 24(8):240-242.
[10]	Schmittgen TD, Zakrajsek BA, Mills AG, et al.Quantitative reverse transcription- polymerase chain reaction to study mRNA decay: comparison of endpoint and real-time methods[J]. Anal Biochem, 2000,285(2):194-204.
[11]	Ieclercq IA, da Silva Morais A, Schroyen B, et al. Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences[J]. J Hepatol, 2007, 47(1):142-156.
[12]	Hotamisligil GS.Inflammation and metabolic disorders[J]. Nature, 2006, 444(7121): 860-867.
[13]	Eizirik DL, Colli ML, Ortis F.The role of inflammation in insulitis and β-cell loss in type 1 diabetes[J]. Nat Rev Endocrinol, 2009, 5(4):219-226.
[14]	Dogusan Z, Garcia M, Flamez D, et al.Double-stranded RNA induces pancreatic beta cell apoptosis by activation of the TLR3 and INF-β pathways[J]. Diabetes, 2008, 57(5):1236-1245.
[15]	Shi H, Kokoeva MV, Inouye K. et a1. TLR4 links innate Immunity and fatty acid-induced insulin resistance[J]. J Clin Invest, 2006, 116(11): 3015-3025.
[16]	Kim F, Pham M, Luttrell I, et al.Diet-Induced obesity toll-Like receptor-4 mediates vascular inflammation and insulin resistance in Diet-Induced Obesity[J]. Circ Res, 2007, 100(11): 1589-1596.
[17]	赵保胜, 高晓燕, 刘洋, 等. 桑叶治疗2型糖尿病药效及其机理研究[J]. 中国实验方剂学杂志, 2012, 18(20): 263-266.
[18]	赵保胜, 刘洋, 高晓燕, 等. 棕榈酸对C2C12细胞Toll样受体及其炎症因子表达的影响[J]. 中国临床药理学与治疗学, 2012, 17(11): 1201-1205.