消渴脂平胶囊对2型糖尿病大鼠糖脂代谢及肝脏组织NF-κB的影响
|
摘要
目的:本文从文献综述、理论探讨、实验研究方面对消渴脂平胶囊防治T2DM、IR进行较系统的研究。重点阐述了肝内炎症是T2DM、IR的发病机理,探讨了益气养阴,化瘀泻浊理论与T2DM、IR肝内炎症发病机制的相关性。通过实验研究观察了消渴脂平胶囊通过抑制肝内NF-κB的表达,从而改善IR,进而起到防治T2DM的作用,从理论和实验上发挥了中医药在防治T2DM、IR上的优势。
方法:本实验建立T2DM大鼠模型,分为正常组、模型组、消渴脂平胶囊治疗组、马来酸罗格列酮治疗组。进行血糖、血脂、CRP相关指标的检测,并采用免疫组化法,从蛋白水平观察各组肝脏组织中NF-κB表达的情况。
结果:1、消渴脂平胶囊可降低T2DM大鼠的一般状态,具有降血糖的作用,与T2DM模型组比较有显著性统计学意义(P<0.01);能减轻肥胖大鼠体质量,与T2DM模型组比较有显著性统计学意义(P<0.01);具有降低血清胆固醇(CHO)、甘油三酯(TG)的作用,与DM模型组比较有显著性统计学意义(P<0.01)。提示消渴脂平胶囊对实验性T2DM大鼠具有良好的调节糖脂代谢作用。2、消渴脂平胶囊可降低T2DM大鼠C反应蛋白水平,与模型组比具有显著性差异。提示消渴脂平胶囊可改善T2DM大鼠机体内的微炎症环境。3、T2DM大鼠肝脏组织中NF-κB蛋白表达情况:免疫组化结果显示,消渴脂平胶囊组NF-κB阳性反应产物主要表达于库普弗细胞核、肝内浸润的炎症细胞核、肝脂滴小泡壁及少数肝细胞核,但受累细胞数和染色强度低于模型组。模型组NF-κB阳性反应产物主要表达于库普弗细胞核、肝内浸润的炎症细胞核、肝脂滴小泡壁及少数肝细胞核,染色浓重、累及范围广。
结论:1、消渴脂平胶囊具有降血糖、降血脂、减轻体重和改善IR的作用。2、T2DM大鼠肝脏组织中NF-κB蛋白表达水平升高,提示NF-κB可能是肥胖T2DM肝脏组织微炎症的发病环节之一;消渴脂平胶囊可降低T2DM大鼠肝脏组织中NF-κB蛋白表达水平,说明NF-κB可能是该中药复方的作用靶点。
Objective:This article from the literature review, theoretical discussion, experimental research on Xiaokezhipingjiaonang prevention and control T2DM, IR a more systematic study. Focuses on the liver inflammation is T2DM, IR pathogenesis, discusses the Yiqiyangyin, Huayuxiezhuo theory and T2DM, IR intrahepatic inflammatory pathogenesis of relevance. Observed through experimen Xiaokezhipingjiaonang by inhibiting the expression of liver NF-κB, thereby improving IR, and thus play a role in T2DM prevention from theory and experiment played a Chinese medicine in the prevention and control T2DM, IR on advantage.
Methods:This study established rat model of T2DM were divided into normal group, model group, Xiaokezhipingjiaonang group, rosiglitazone maleate in the treatment group. Blood glucose, blood lipids, CRP detection of relevant indicators, and using immunohistochemistry, protein levels were observed from the liver expression of NF-κB in the case.
Results: 1. Xiaokezhipingjiaonang be reduced lipid levels in rats of the general state of T2DM, the ability to reduce blood sugar, and T2DM model group was significant statistical significance (P<0.01); can reduce body weight in obese rats with T2DM model group was significant statistical significance (P<0.01); with lower serum cholesterol (CHO), triglyceride Cool (TG) role, with the DM model group were significantly statistically significant (P<0.01). Xiaokezhipingjiaonang in experimental rats with good regulation T2DM lipid metabolism. 2. Xiaokezhipingjiaonang be reduced T2DM rat C-reactive protein level, with the model group were significant differences. Tip Xiaokezhipingjiaonang only improve lipid levels in rats T2DM micro-inflammation in the body environment. 3. T2DM rat liver NF-κB protein expression: immunohistochemistry results showed that: Xiaokezhipingjiaonang group NF-kB-positive reaction product was mainly expressed in Kupffer cell nucleus, nuclear inflammatory infiltration of the liver, liver and small lipid droplets Cell wall and a few liver cells, but affected cell number and staining intensity model than the model group. Model group, the NF-kB-positive reaction product was mainly expressed in Kupffer cell nucleus, nuclear inflammatory infiltration of the liver, liver lipid droplets in alveolar walls and a few liver cells, strong staining, involving a wide range.
Conclusion: 1. Xiaokezhipingjiaonang have lower blood sugar,blood fat,reduce weight and improve the IR role. 2.T2DM rat liver tissue expression of NF-κB protein levels,suggesting that NF-κB may be obese T2DM pathogenesis of liver inflammation in one of the links micro; Xiaokezhipingjiaonang before rat liver tissue of T2DM NF-κB protein levels,indicating that NF-κB may be a target of the role of Chinese medicine.
方法:本实验建立T2DM大鼠模型,分为正常组、模型组、消渴脂平胶囊治疗组、马来酸罗格列酮治疗组。进行血糖、血脂、CRP相关指标的检测,并采用免疫组化法,从蛋白水平观察各组肝脏组织中NF-κB表达的情况。
结果:1、消渴脂平胶囊可降低T2DM大鼠的一般状态,具有降血糖的作用,与T2DM模型组比较有显著性统计学意义(P<0.01);能减轻肥胖大鼠体质量,与T2DM模型组比较有显著性统计学意义(P<0.01);具有降低血清胆固醇(CHO)、甘油三酯(TG)的作用,与DM模型组比较有显著性统计学意义(P<0.01)。提示消渴脂平胶囊对实验性T2DM大鼠具有良好的调节糖脂代谢作用。2、消渴脂平胶囊可降低T2DM大鼠C反应蛋白水平,与模型组比具有显著性差异。提示消渴脂平胶囊可改善T2DM大鼠机体内的微炎症环境。3、T2DM大鼠肝脏组织中NF-κB蛋白表达情况:免疫组化结果显示,消渴脂平胶囊组NF-κB阳性反应产物主要表达于库普弗细胞核、肝内浸润的炎症细胞核、肝脂滴小泡壁及少数肝细胞核,但受累细胞数和染色强度低于模型组。模型组NF-κB阳性反应产物主要表达于库普弗细胞核、肝内浸润的炎症细胞核、肝脂滴小泡壁及少数肝细胞核,染色浓重、累及范围广。
结论:1、消渴脂平胶囊具有降血糖、降血脂、减轻体重和改善IR的作用。2、T2DM大鼠肝脏组织中NF-κB蛋白表达水平升高,提示NF-κB可能是肥胖T2DM肝脏组织微炎症的发病环节之一;消渴脂平胶囊可降低T2DM大鼠肝脏组织中NF-κB蛋白表达水平,说明NF-κB可能是该中药复方的作用靶点。
Objective:This article from the literature review, theoretical discussion, experimental research on Xiaokezhipingjiaonang prevention and control T2DM, IR a more systematic study. Focuses on the liver inflammation is T2DM, IR pathogenesis, discusses the Yiqiyangyin, Huayuxiezhuo theory and T2DM, IR intrahepatic inflammatory pathogenesis of relevance. Observed through experimen Xiaokezhipingjiaonang by inhibiting the expression of liver NF-κB, thereby improving IR, and thus play a role in T2DM prevention from theory and experiment played a Chinese medicine in the prevention and control T2DM, IR on advantage.
Methods:This study established rat model of T2DM were divided into normal group, model group, Xiaokezhipingjiaonang group, rosiglitazone maleate in the treatment group. Blood glucose, blood lipids, CRP detection of relevant indicators, and using immunohistochemistry, protein levels were observed from the liver expression of NF-κB in the case.
Results: 1. Xiaokezhipingjiaonang be reduced lipid levels in rats of the general state of T2DM, the ability to reduce blood sugar, and T2DM model group was significant statistical significance (P<0.01); can reduce body weight in obese rats with T2DM model group was significant statistical significance (P<0.01); with lower serum cholesterol (CHO), triglyceride Cool (TG) role, with the DM model group were significantly statistically significant (P<0.01). Xiaokezhipingjiaonang in experimental rats with good regulation T2DM lipid metabolism. 2. Xiaokezhipingjiaonang be reduced T2DM rat C-reactive protein level, with the model group were significant differences. Tip Xiaokezhipingjiaonang only improve lipid levels in rats T2DM micro-inflammation in the body environment. 3. T2DM rat liver NF-κB protein expression: immunohistochemistry results showed that: Xiaokezhipingjiaonang group NF-kB-positive reaction product was mainly expressed in Kupffer cell nucleus, nuclear inflammatory infiltration of the liver, liver and small lipid droplets Cell wall and a few liver cells, but affected cell number and staining intensity model than the model group. Model group, the NF-kB-positive reaction product was mainly expressed in Kupffer cell nucleus, nuclear inflammatory infiltration of the liver, liver lipid droplets in alveolar walls and a few liver cells, strong staining, involving a wide range.
Conclusion: 1. Xiaokezhipingjiaonang have lower blood sugar,blood fat,reduce weight and improve the IR role. 2.T2DM rat liver tissue expression of NF-κB protein levels,suggesting that NF-κB may be obese T2DM pathogenesis of liver inflammation in one of the links micro; Xiaokezhipingjiaonang before rat liver tissue of T2DM NF-κB protein levels,indicating that NF-κB may be a target of the role of Chinese medicine.
引文
[1]徐凌.糖尿病从脾胃论治浅谈[J].江苏中医,2001,22(9):8.
[2]贺文广,杨竞,王栋,等.糖尿病从脾胃论治[J].山东中医杂志,2005,24(4):202-203.
[3]赵翠芳,关崧,刘铜华.从脾胃论治在中医诊治糖尿病中的地位和作用[J].北京中医药大学学报(中医临床版),2009,16(3):38-40.
[4]张彦丽.肝与消渴刍议[J].中医药导报,2009,15(10):10-12.
[5]冯建文.从肝论治糖尿病理论基础的探讨[J].江苏中医药,2009,41(10):61-62.
[6]郭会军,吕爱平.中医脾肾与糖尿病发病关系初探[J].辽宁中医药大学学报,2009,11(8):81-82.
[7]王自润.肾虚在消渴发病中的作用[J].中华中医药学刊,2008,26(7):1403-1404.
[8]林晓天.从痰湿论治消渴[J].陕西中医,2007,28(7):935-936.
[9]仝小林,李洪皎.治胖新思路:驱除“膏浊”之毒[J].糖尿病之友,2006,5:46-47.
[10]常柏,刘喜明,甄仲,等.肥胖2型糖尿病的病因病机及证治规律初探[J].北京中医药,2008,27,12:946-947.
[11]孙立,郑博庆,朱秉匡.脾肾两虚、痰瘀互结与糖尿病发病机理的探讨[J].时珍国医国药,2005,16(9):912-914.
[12]张健.从脾论治胰岛素抵抗[J].河北中医,2007,29(2):132-133.
[13]刘承琴,赵建群.2型糖尿病胰岛素抵抗重视从脾论治的思路[J].新中医,2003,35(9):28-29.
[14]第五永长,许建秦.胰岛素抵抗中医病机探讨[J].四川中医,2008,26(1):8-10.
[15]于淼,朴春丽,南征.2型糖尿病胰岛素抵抗从毒损肝络论治的理论初探[J].上海中医药杂志,2007,41(3):18-20.
[16]王智明.胰岛素抵抗从肝论治的探讨[J].光明中医,2003,18(6):13.
[17]吉训超,谢志雄,刘艳霞,等.2型糖尿病胰岛素抵抗的中医实质初探[J].新中医,2005,37(7):88-89.
[18]黄冬梅,陆付耳,黄光英.补肾通脉方对胰岛素抵抗大鼠胰岛素信号转导的影响[J].中国中西医结合杂志,2003,23,(9):684.
[19]钱毅,薛耀明,李佳,等.六味地黄丸对自发性2型糖尿病大鼠血浆脂联素水平的影响[J].南方医科大学学报,2008,28(1):34.
[20]刘承琴,赵建群.2型糖尿病胰岛素抵抗重视从脾论治的思路[J].新中医, 2003,35(9):28-29.
[21]杨文军,郭宝荣,赵泉霖.中药配合口服降糖药对2型糖尿病患者胰岛素抵抗及微量蛋白尿的影响[J].山东中医药大学学报,2003,27(7):285-286.
[22]江南,刘铜华.胰岛素抵抗的中医病机探讨[J].中国中医基础医学杂志,2006,12(9):690-692.
[23]李怡,闰小光.中医药对胰岛素抵抗的研究现状[J].中草药,2005,36(5):793.
[24]朱良,争钟家宝,徐蓉绢.降脂片改善II型糖尿病胰岛素抵抗的临床观察[J].新中医,1999,31(4):13-16.
[25]周则卫.II型糖尿病发生胰岛素抵抗机理的中医探讨[J].天津中医,2002,8(19):38-39.
[26]白卫莲,赵莉娟.糖尿病从血瘀论治思路探讨[J].世界中西医结合杂志,2010,5(10):900-902.
[27]林兰.糖尿病中医证治研究[M].北京:海洋出版社,2000:1-3.
[28]蒙杏泽,朱小晓.中医辨证分型对胰岛素抵抗的早期干预治疗50例观察[J].中国医药导报,2006,3(24):105.
[29]阮永队,陈红梅,莫冰泉,等.中医温阳健脾法与降糖药合用治疗2型糖尿病胰岛素抵抗阳虚证[J].广州中医药大学学报,2007,24(3):184-186.
[30]周国英,武雪萍,衡先培,等.II型糖尿病气阴两虚证与胰岛素抵抗的相关性研究[J].福建中医药,2000,31(2):8.
[31]徐成兴,叶伟成,胡蕴刚.120例2型糖尿病患者的中医辨证分型及相关分析[J].上海中医药杂志,2007,41(6):34.
[32]陈思兰,林兰,楚晓燕,等.2型糖尿病中医辨证分型与胰岛素抵抗的相关性分析[J].中国中医药信息杂志,2001,8(6):49-51.
[33]周金虎,姚定国,李欣.2型糖尿病中医辨证分型与胰岛素抵抗及生长抑素的关系[J].浙江中西医结合杂志,2009,18(4):204-205.
[34] TOSHIRO M,SUMI E,TOMOKO F, et al.Strong and tihyperglycemic effects Of water-soluble fraction of Brazilian propolis and its bioactive constituent,3,4,5-tri-o-caffeoylquinic acid[J].Biological& Pharmaceutical Bulletin,2004,27(11):1797-1803.
[35] HAVSTEEN B H.The biochemistry and medical significance of the flavonoids[J].Pharmacology&Therapeutics,2002,96:67-202.
[36]李雅晶,胡福良,称民利.蜂胶对糖脂代谢的调节作用及机制研究进展[J].中草药,2007,38(10):1593-1596.
[37]原爱红,马骏,蒋晓峰,等.桑叶中糖苷酶抑制活性组分的筛选[J].中国中药杂志,2006,31(3):223-227.
[38]李宏,黄金山,胡浩,等.桑叶对α-葡萄糖苷酶活力的影响及降糖机理的研究[J].中国蚕业,2003,24(2):19-21.
[39]马运明,李大鸣,张静,等.葛根素对糖尿病小鼠降血糖功能的研究[J].中国慢性病预防与控制,2010,18,(4):373-374.
[40]刘蕴玲,陈少华,陈秀彬.葛根素对Ⅱ型糖尿病人胰岛素敏感性的影响[J].辽宁实用糖尿病杂志,2000,8(1):26-28.
[41]钟艺,谭海荣,潘竞锵,等.葛根素对D-半乳糖诱导大鼠抑制蛋白非酶糖基化及增强胰岛素敏感性的作用[J].中国药物与临床,2007,7(8):576-579.
[42]龚志刚,胡红霞,朱笃,等.葛根素对糖尿病大鼠血糖和抗氧化能力的影响[J].营养卫生,2006,27(11):498-501.
[43]夏卫军,程海波,张莉.鬼箭羽治疗2型糖尿病实验研究[J].陕西中医,2001,22(8):505.
[44]高媛,方宪康.RP-HPLC法测定鬼箭羽中3种活性成分的含量[J].中华中医药学刊,2007,7(25):1441.
[45]杨海燕.中药鬼箭羽提取物对脂肪细胞葡萄糖摄取作用的影响[J].中国天然药物,2004,2(6):365-368.
[46]金椿,戴瑞鸿,周峰等.黄芪对冠心病患者红细胞内钠含量和钠转运的影响[J].中西医结合杂志,1991,11(11):651-653.
[47]兰艳玲,宋淑梅,米洪滨等.益肾消渴方促胰岛素分泌作用的研究[J].中医药学报,1998,14(1):58-59.
[48]熊曼琪,林安钟,朱章志,等.加味桃核承气汤对Ⅱ型糖尿病大鼠胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(3):165-168.
[49]赵保胜,赵威,王秀丽,等.人参白虎汤治疗糖尿病药效及其机理研究[J].中药新药与临床药理,2010,21(5):493-496.
[50]朴春丽,杨叔禹,仝小林,等.解毒通络调肝法对实验性糖尿病大鼠肝脏IRS-2表达的影响[J].中华实用中西医杂志,2009,22(14):1176-1179.
[51]陆灏,叶伟成,丁学屏.三黄片对胰岛素抵抗大鼠TNF-α、FFA的影响[J].浙江中西医结合杂志,2003,13(12):750-751.
[52]陆付耳,冷三华,屠庆年,等.黄连解毒汤与黄连素对2型糖尿病大鼠葡萄糖和脂质代谢影响的比较研究[J].华中科技大学学报(医学版),2002,31(6):662-665.
[53]谭燚,陆付耳,徐丽君,等.黄连解毒汤对2型糖尿病大鼠细胞因子IL-4和IL-10水平的影响[J].微循环学杂志,2005,15(3):44-45,49.
[54]石巧荣,田进文,王丽英.2型糖尿病与炎症及抗炎治疗进展[J].实用医学杂志,2007,23(15):2289-2290.
[55]邹丽霞,谷卫.环氧化酶-2与糖尿病[J].国际内分泌代谢杂志,2006,26(1):45-47.
[56]杨丽娟,母义明.2糖尿病与炎症及抗炎疗法[J].实用糖尿病杂志,2006,2(2):4-7.
[57]牛洁,刘铜华.炎症与胰岛素抵抗关系研究概况[J].深圳中西医结合杂志,2008,18(2):116-119.
[58]方丹,刘红.IκB激酶在炎症与2型糖尿病中的作用[J].实用医学杂志,2008,24(20): 3616-3617.
[59] He J,Usui I,Ishizuka K,et a1.Interleukin-lαinhibits insulin signaling with phosphor-ylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes[J].Mol Endocrinol,2006,20(1):114-124.
[60] Nakamori Y,Emoto M,Fukuda N,et a1.Myosin motor Myolc and its receptor NEMO/IKK-gamma promote TNF-α-induced serine307 phospho-rylation of IRS[J].Cell Biol,2006,173(5):665-671.
[61]周媛,刘保林,唐宁.胰岛素抵抗的炎症机制及治疗研究进展[J].海峡药学,2008,20(4):10-13.
[62]任晓军,冯凭.炎症因子与胰岛素抵抗[J].中国实用医刊,2008,35(11):82-84.
[63]徐艳,高燕玲,孙峰.炎症因子与2型糖尿病胰岛素抵抗的相关性研究[J].临床荟萃, 2007,22(2):114-115.
[64]盛志新.炎症与2型糖尿病的关系[J].新医学,2008,39(5):345-347.
[65]刘开泰,韩秀敏,张阳.IκB激酶结构和功能研究进展[J].大连医科大学学报,2007,29(1):85-88.
[66] Stephen,Susar.Management of Diabetes and Hyperglycemia inHospitals,Diabetes Care,2004,27(2):553-591.
[67]王艳军,赵晟,姜苒华,刘国良.核因子κB在胰岛素抵抗大鼠动脉内皮细胞的表达及意义[J].中国老年学杂志,2008,5(28):845-847.
[68] Srinivasan K,Viswanad B,Asrat L,et al.Combination of high-fat diet-fed and low- dose streptozotocin-treated rat:amodel for type 2 diabetes and pharmacological screening[J].PharmacolRes,2005,52(4):313-20.
[69]周迎生,高妍,李斌,等.高脂喂养联合链脲佐菌素注射的糖尿病大鼠模型特征[J].中国实验动物学报,2005,13(3):154-8.
[70] Chavez JA,Knotts TA,Mang LP,et al.A role for ceramide,but not diary glycerol inthe antagonism of insulin signal transduction by saturated fatty acids[J].J Biol- Chem,2003,13:10297-10303.
[71] Gorska M,Dobrzyn A,Zendzian-Piotrowska M,et al.Effect of Streptozotoe in-Diabetes on the functioning of the springy myelin-signaling pathway in skeletal muscles of the rat[J].Horm Metab Res,2004,36:14-21.
[72] Straczkowski M,Kowalska I,Nikolajuk A,et al.Relationship between insulin sensitivity and springy myelin signaling pathway in human skeletal muscle[J].Diabetes, 2004,53:1215-1221.
[73]孙雪东,刘春艳,陈牛燕,等.消渴宁对2型糖尿病大鼠糖代谢和脂代谢的影响[J].中国中医药信息杂志,2009,16(2):41-42.
[74]周兴建,蒋绿芝.MCP-1与胰岛素抵抗和2型糖尿病的关系[J].国际内分泌代谢杂志,2006,26(2):99-101.
[75]刘庆生,陈芝芸,严茂祥,等.理气化痰祛癖中药复方对非酒精性脂肪肝大鼠肝组织NF-кB、IкB a表达的影响[J].中国中医药科技,2006,13(3):146-148.
[76]李山,李洪忠.对“阴虚为本,燥实为标”是消渴发病的主要病理变化的探讨[J].工企医刊,2007,20(5):39-40.
[77]岳仁宋,王帅,员富圆,等.2型糖尿病的中医分期分型辨证探析[J].辽宁中医杂志,2010,37(10):1917-1918.
[78]吴童.古代文献中消渴病的主要病机[J].中国中医基础医学杂志,2007,13(8):577-578.
[79]柴伟栋,陈家伟.微循环与糖尿病微血管病变[J].中国微循环,2000,4(2):130.
[80]仝小林,胡洁,李洪皎,等.糖尿病中医新论[J].中华中医药杂志,2006,21(6):349-352.
[81] McGarry JD.Dysregulation of fatty acid metabolism in the etiolog of type 2 diabetes[J].Diabetes,2002,51(1):7-18.
[82] Chavez JA,Knotts TA,Mang LP,et al.A role for ceramide,but not diary glycerol inthe antagonism of insulin signal transduction by saturated fatty acids[J].J Biol- Chem,2003,13:10297-10303.
[83] Gorska M,Dobrzyn A,Zendzian-Piotrowska M,et al.Effect of Streptozotoe in-Diabetes on the functioning of the springy myelin-signaling pathway in skeletal muscles of the rat [J].Horm Metab Res,2004,36:14-21.
[84] Straczkowski M,Kowalska I,Nikolajuk A,et al.Relationship between insulin sensitivity and springy myelin signaling pathway in human skeletal muscle[J].Diabetes, 2004,53:1215-1221.
[85]中华中医药学会糖尿病分会.糖尿病中医防治指南[M].北京:中国中医药出版社, 2007:1-3.
[86]刘喜明.试论消渴病临床面貌与概念的变化[J].世界中西医结合杂志,2007,2(4):187- 189.
[87]都健,曾芙蓉.空腹血糖受损人群血清C反应蛋白表达及临床意义探讨[J].中国实用内科杂志,2006,26:431-432.
[88] Barbara BK,Jeffrey S.Flier Obesity and insulin resistance[J].The Journal of Clinical Investigation,2000,8 (106):473-81.
[89] Fernndez-Real JM,Ricart W.Insulin resistance and chronic cardiovascular inflamma -tory syndrome[J] .Endocrine Reviews,2003,24 (3):278-301.
[90] Freeman D J,Norrie J,Caslake M J,et al.C-reactive protein is an independent predictor of risk for the development of diabetes in the west of Scotland Cornory Prevention Study[J].Diabetes,2002,51(5):1596-1600.
[91] Hu F B,Meigs J B,Li T Y,et al.Inflammatory markers and risk of developing type 2 diabetes in women[J].Diabetes,2004,53(3):693-700.
[92]徐艳,高燕玲,孙峰.炎症因子与2型糖尿病胰岛素抵抗的相关性研究[J].临床荟萃, 2007,22(2):114-115.
[93]陆君.慢性炎症与2型糖尿病[J].实用心脑肺血管病杂志,2006,14(8):600-602.
[94] Mroz RM,Noparlik J,Chyczewska E,el a1.Molecular basis of chronic in flammation in lung diseases:new therapeutic approach[J].J Physiol Pharmacol,2007,58 suppl 5(Pt2):453-460.
[95]陈红,孙明杰,彭娟,等.黄连解毒汤对糖尿病大鼠肝脏核因子-κB、肿瘤坏死因子-α表达的影响[J].中国实验方剂学杂志,2010,16(18):153-156.
[96] Ghanim H,Aljada A,Hofmeyer D,et al.Circulating mononuclear cells in the obese are in a proinflamm atory state[J] .Circulation,2004,110(12):1564-1571.
[97]石秀林,李芳萍,蔡梦茵,等.新诊断2型糖尿病患者血清炎症因子及外周血单个核细胞中核因子κB活性变化[J].中山大学学报医学科学版,2006,27(3):266-270.
[98]于淼,朴春丽,南征,等.2型糖尿病胰岛素抵抗的肝内炎症发病机制与毒损肝络病机制论的相关性探讨[J].中国中西医结合杂志,2006,26(11):1032.
[2]贺文广,杨竞,王栋,等.糖尿病从脾胃论治[J].山东中医杂志,2005,24(4):202-203.
[3]赵翠芳,关崧,刘铜华.从脾胃论治在中医诊治糖尿病中的地位和作用[J].北京中医药大学学报(中医临床版),2009,16(3):38-40.
[4]张彦丽.肝与消渴刍议[J].中医药导报,2009,15(10):10-12.
[5]冯建文.从肝论治糖尿病理论基础的探讨[J].江苏中医药,2009,41(10):61-62.
[6]郭会军,吕爱平.中医脾肾与糖尿病发病关系初探[J].辽宁中医药大学学报,2009,11(8):81-82.
[7]王自润.肾虚在消渴发病中的作用[J].中华中医药学刊,2008,26(7):1403-1404.
[8]林晓天.从痰湿论治消渴[J].陕西中医,2007,28(7):935-936.
[9]仝小林,李洪皎.治胖新思路:驱除“膏浊”之毒[J].糖尿病之友,2006,5:46-47.
[10]常柏,刘喜明,甄仲,等.肥胖2型糖尿病的病因病机及证治规律初探[J].北京中医药,2008,27,12:946-947.
[11]孙立,郑博庆,朱秉匡.脾肾两虚、痰瘀互结与糖尿病发病机理的探讨[J].时珍国医国药,2005,16(9):912-914.
[12]张健.从脾论治胰岛素抵抗[J].河北中医,2007,29(2):132-133.
[13]刘承琴,赵建群.2型糖尿病胰岛素抵抗重视从脾论治的思路[J].新中医,2003,35(9):28-29.
[14]第五永长,许建秦.胰岛素抵抗中医病机探讨[J].四川中医,2008,26(1):8-10.
[15]于淼,朴春丽,南征.2型糖尿病胰岛素抵抗从毒损肝络论治的理论初探[J].上海中医药杂志,2007,41(3):18-20.
[16]王智明.胰岛素抵抗从肝论治的探讨[J].光明中医,2003,18(6):13.
[17]吉训超,谢志雄,刘艳霞,等.2型糖尿病胰岛素抵抗的中医实质初探[J].新中医,2005,37(7):88-89.
[18]黄冬梅,陆付耳,黄光英.补肾通脉方对胰岛素抵抗大鼠胰岛素信号转导的影响[J].中国中西医结合杂志,2003,23,(9):684.
[19]钱毅,薛耀明,李佳,等.六味地黄丸对自发性2型糖尿病大鼠血浆脂联素水平的影响[J].南方医科大学学报,2008,28(1):34.
[20]刘承琴,赵建群.2型糖尿病胰岛素抵抗重视从脾论治的思路[J].新中医, 2003,35(9):28-29.
[21]杨文军,郭宝荣,赵泉霖.中药配合口服降糖药对2型糖尿病患者胰岛素抵抗及微量蛋白尿的影响[J].山东中医药大学学报,2003,27(7):285-286.
[22]江南,刘铜华.胰岛素抵抗的中医病机探讨[J].中国中医基础医学杂志,2006,12(9):690-692.
[23]李怡,闰小光.中医药对胰岛素抵抗的研究现状[J].中草药,2005,36(5):793.
[24]朱良,争钟家宝,徐蓉绢.降脂片改善II型糖尿病胰岛素抵抗的临床观察[J].新中医,1999,31(4):13-16.
[25]周则卫.II型糖尿病发生胰岛素抵抗机理的中医探讨[J].天津中医,2002,8(19):38-39.
[26]白卫莲,赵莉娟.糖尿病从血瘀论治思路探讨[J].世界中西医结合杂志,2010,5(10):900-902.
[27]林兰.糖尿病中医证治研究[M].北京:海洋出版社,2000:1-3.
[28]蒙杏泽,朱小晓.中医辨证分型对胰岛素抵抗的早期干预治疗50例观察[J].中国医药导报,2006,3(24):105.
[29]阮永队,陈红梅,莫冰泉,等.中医温阳健脾法与降糖药合用治疗2型糖尿病胰岛素抵抗阳虚证[J].广州中医药大学学报,2007,24(3):184-186.
[30]周国英,武雪萍,衡先培,等.II型糖尿病气阴两虚证与胰岛素抵抗的相关性研究[J].福建中医药,2000,31(2):8.
[31]徐成兴,叶伟成,胡蕴刚.120例2型糖尿病患者的中医辨证分型及相关分析[J].上海中医药杂志,2007,41(6):34.
[32]陈思兰,林兰,楚晓燕,等.2型糖尿病中医辨证分型与胰岛素抵抗的相关性分析[J].中国中医药信息杂志,2001,8(6):49-51.
[33]周金虎,姚定国,李欣.2型糖尿病中医辨证分型与胰岛素抵抗及生长抑素的关系[J].浙江中西医结合杂志,2009,18(4):204-205.
[34] TOSHIRO M,SUMI E,TOMOKO F, et al.Strong and tihyperglycemic effects Of water-soluble fraction of Brazilian propolis and its bioactive constituent,3,4,5-tri-o-caffeoylquinic acid[J].Biological& Pharmaceutical Bulletin,2004,27(11):1797-1803.
[35] HAVSTEEN B H.The biochemistry and medical significance of the flavonoids[J].Pharmacology&Therapeutics,2002,96:67-202.
[36]李雅晶,胡福良,称民利.蜂胶对糖脂代谢的调节作用及机制研究进展[J].中草药,2007,38(10):1593-1596.
[37]原爱红,马骏,蒋晓峰,等.桑叶中糖苷酶抑制活性组分的筛选[J].中国中药杂志,2006,31(3):223-227.
[38]李宏,黄金山,胡浩,等.桑叶对α-葡萄糖苷酶活力的影响及降糖机理的研究[J].中国蚕业,2003,24(2):19-21.
[39]马运明,李大鸣,张静,等.葛根素对糖尿病小鼠降血糖功能的研究[J].中国慢性病预防与控制,2010,18,(4):373-374.
[40]刘蕴玲,陈少华,陈秀彬.葛根素对Ⅱ型糖尿病人胰岛素敏感性的影响[J].辽宁实用糖尿病杂志,2000,8(1):26-28.
[41]钟艺,谭海荣,潘竞锵,等.葛根素对D-半乳糖诱导大鼠抑制蛋白非酶糖基化及增强胰岛素敏感性的作用[J].中国药物与临床,2007,7(8):576-579.
[42]龚志刚,胡红霞,朱笃,等.葛根素对糖尿病大鼠血糖和抗氧化能力的影响[J].营养卫生,2006,27(11):498-501.
[43]夏卫军,程海波,张莉.鬼箭羽治疗2型糖尿病实验研究[J].陕西中医,2001,22(8):505.
[44]高媛,方宪康.RP-HPLC法测定鬼箭羽中3种活性成分的含量[J].中华中医药学刊,2007,7(25):1441.
[45]杨海燕.中药鬼箭羽提取物对脂肪细胞葡萄糖摄取作用的影响[J].中国天然药物,2004,2(6):365-368.
[46]金椿,戴瑞鸿,周峰等.黄芪对冠心病患者红细胞内钠含量和钠转运的影响[J].中西医结合杂志,1991,11(11):651-653.
[47]兰艳玲,宋淑梅,米洪滨等.益肾消渴方促胰岛素分泌作用的研究[J].中医药学报,1998,14(1):58-59.
[48]熊曼琪,林安钟,朱章志,等.加味桃核承气汤对Ⅱ型糖尿病大鼠胰岛素抵抗的影响[J].中国中西医结合杂志,1997,17(3):165-168.
[49]赵保胜,赵威,王秀丽,等.人参白虎汤治疗糖尿病药效及其机理研究[J].中药新药与临床药理,2010,21(5):493-496.
[50]朴春丽,杨叔禹,仝小林,等.解毒通络调肝法对实验性糖尿病大鼠肝脏IRS-2表达的影响[J].中华实用中西医杂志,2009,22(14):1176-1179.
[51]陆灏,叶伟成,丁学屏.三黄片对胰岛素抵抗大鼠TNF-α、FFA的影响[J].浙江中西医结合杂志,2003,13(12):750-751.
[52]陆付耳,冷三华,屠庆年,等.黄连解毒汤与黄连素对2型糖尿病大鼠葡萄糖和脂质代谢影响的比较研究[J].华中科技大学学报(医学版),2002,31(6):662-665.
[53]谭燚,陆付耳,徐丽君,等.黄连解毒汤对2型糖尿病大鼠细胞因子IL-4和IL-10水平的影响[J].微循环学杂志,2005,15(3):44-45,49.
[54]石巧荣,田进文,王丽英.2型糖尿病与炎症及抗炎治疗进展[J].实用医学杂志,2007,23(15):2289-2290.
[55]邹丽霞,谷卫.环氧化酶-2与糖尿病[J].国际内分泌代谢杂志,2006,26(1):45-47.
[56]杨丽娟,母义明.2糖尿病与炎症及抗炎疗法[J].实用糖尿病杂志,2006,2(2):4-7.
[57]牛洁,刘铜华.炎症与胰岛素抵抗关系研究概况[J].深圳中西医结合杂志,2008,18(2):116-119.
[58]方丹,刘红.IκB激酶在炎症与2型糖尿病中的作用[J].实用医学杂志,2008,24(20): 3616-3617.
[59] He J,Usui I,Ishizuka K,et a1.Interleukin-lαinhibits insulin signaling with phosphor-ylating insulin receptor substrate-1 on serine residues in 3T3-L1 adipocytes[J].Mol Endocrinol,2006,20(1):114-124.
[60] Nakamori Y,Emoto M,Fukuda N,et a1.Myosin motor Myolc and its receptor NEMO/IKK-gamma promote TNF-α-induced serine307 phospho-rylation of IRS[J].Cell Biol,2006,173(5):665-671.
[61]周媛,刘保林,唐宁.胰岛素抵抗的炎症机制及治疗研究进展[J].海峡药学,2008,20(4):10-13.
[62]任晓军,冯凭.炎症因子与胰岛素抵抗[J].中国实用医刊,2008,35(11):82-84.
[63]徐艳,高燕玲,孙峰.炎症因子与2型糖尿病胰岛素抵抗的相关性研究[J].临床荟萃, 2007,22(2):114-115.
[64]盛志新.炎症与2型糖尿病的关系[J].新医学,2008,39(5):345-347.
[65]刘开泰,韩秀敏,张阳.IκB激酶结构和功能研究进展[J].大连医科大学学报,2007,29(1):85-88.
[66] Stephen,Susar.Management of Diabetes and Hyperglycemia inHospitals,Diabetes Care,2004,27(2):553-591.
[67]王艳军,赵晟,姜苒华,刘国良.核因子κB在胰岛素抵抗大鼠动脉内皮细胞的表达及意义[J].中国老年学杂志,2008,5(28):845-847.
[68] Srinivasan K,Viswanad B,Asrat L,et al.Combination of high-fat diet-fed and low- dose streptozotocin-treated rat:amodel for type 2 diabetes and pharmacological screening[J].PharmacolRes,2005,52(4):313-20.
[69]周迎生,高妍,李斌,等.高脂喂养联合链脲佐菌素注射的糖尿病大鼠模型特征[J].中国实验动物学报,2005,13(3):154-8.
[70] Chavez JA,Knotts TA,Mang LP,et al.A role for ceramide,but not diary glycerol inthe antagonism of insulin signal transduction by saturated fatty acids[J].J Biol- Chem,2003,13:10297-10303.
[71] Gorska M,Dobrzyn A,Zendzian-Piotrowska M,et al.Effect of Streptozotoe in-Diabetes on the functioning of the springy myelin-signaling pathway in skeletal muscles of the rat[J].Horm Metab Res,2004,36:14-21.
[72] Straczkowski M,Kowalska I,Nikolajuk A,et al.Relationship between insulin sensitivity and springy myelin signaling pathway in human skeletal muscle[J].Diabetes, 2004,53:1215-1221.
[73]孙雪东,刘春艳,陈牛燕,等.消渴宁对2型糖尿病大鼠糖代谢和脂代谢的影响[J].中国中医药信息杂志,2009,16(2):41-42.
[74]周兴建,蒋绿芝.MCP-1与胰岛素抵抗和2型糖尿病的关系[J].国际内分泌代谢杂志,2006,26(2):99-101.
[75]刘庆生,陈芝芸,严茂祥,等.理气化痰祛癖中药复方对非酒精性脂肪肝大鼠肝组织NF-кB、IкB a表达的影响[J].中国中医药科技,2006,13(3):146-148.
[76]李山,李洪忠.对“阴虚为本,燥实为标”是消渴发病的主要病理变化的探讨[J].工企医刊,2007,20(5):39-40.
[77]岳仁宋,王帅,员富圆,等.2型糖尿病的中医分期分型辨证探析[J].辽宁中医杂志,2010,37(10):1917-1918.
[78]吴童.古代文献中消渴病的主要病机[J].中国中医基础医学杂志,2007,13(8):577-578.
[79]柴伟栋,陈家伟.微循环与糖尿病微血管病变[J].中国微循环,2000,4(2):130.
[80]仝小林,胡洁,李洪皎,等.糖尿病中医新论[J].中华中医药杂志,2006,21(6):349-352.
[81] McGarry JD.Dysregulation of fatty acid metabolism in the etiolog of type 2 diabetes[J].Diabetes,2002,51(1):7-18.
[82] Chavez JA,Knotts TA,Mang LP,et al.A role for ceramide,but not diary glycerol inthe antagonism of insulin signal transduction by saturated fatty acids[J].J Biol- Chem,2003,13:10297-10303.
[83] Gorska M,Dobrzyn A,Zendzian-Piotrowska M,et al.Effect of Streptozotoe in-Diabetes on the functioning of the springy myelin-signaling pathway in skeletal muscles of the rat [J].Horm Metab Res,2004,36:14-21.
[84] Straczkowski M,Kowalska I,Nikolajuk A,et al.Relationship between insulin sensitivity and springy myelin signaling pathway in human skeletal muscle[J].Diabetes, 2004,53:1215-1221.
[85]中华中医药学会糖尿病分会.糖尿病中医防治指南[M].北京:中国中医药出版社, 2007:1-3.
[86]刘喜明.试论消渴病临床面貌与概念的变化[J].世界中西医结合杂志,2007,2(4):187- 189.
[87]都健,曾芙蓉.空腹血糖受损人群血清C反应蛋白表达及临床意义探讨[J].中国实用内科杂志,2006,26:431-432.
[88] Barbara BK,Jeffrey S.Flier Obesity and insulin resistance[J].The Journal of Clinical Investigation,2000,8 (106):473-81.
[89] Fernndez-Real JM,Ricart W.Insulin resistance and chronic cardiovascular inflamma -tory syndrome[J] .Endocrine Reviews,2003,24 (3):278-301.
[90] Freeman D J,Norrie J,Caslake M J,et al.C-reactive protein is an independent predictor of risk for the development of diabetes in the west of Scotland Cornory Prevention Study[J].Diabetes,2002,51(5):1596-1600.
[91] Hu F B,Meigs J B,Li T Y,et al.Inflammatory markers and risk of developing type 2 diabetes in women[J].Diabetes,2004,53(3):693-700.
[92]徐艳,高燕玲,孙峰.炎症因子与2型糖尿病胰岛素抵抗的相关性研究[J].临床荟萃, 2007,22(2):114-115.
[93]陆君.慢性炎症与2型糖尿病[J].实用心脑肺血管病杂志,2006,14(8):600-602.
[94] Mroz RM,Noparlik J,Chyczewska E,el a1.Molecular basis of chronic in flammation in lung diseases:new therapeutic approach[J].J Physiol Pharmacol,2007,58 suppl 5(Pt2):453-460.
[95]陈红,孙明杰,彭娟,等.黄连解毒汤对糖尿病大鼠肝脏核因子-κB、肿瘤坏死因子-α表达的影响[J].中国实验方剂学杂志,2010,16(18):153-156.
[96] Ghanim H,Aljada A,Hofmeyer D,et al.Circulating mononuclear cells in the obese are in a proinflamm atory state[J] .Circulation,2004,110(12):1564-1571.
[97]石秀林,李芳萍,蔡梦茵,等.新诊断2型糖尿病患者血清炎症因子及外周血单个核细胞中核因子κB活性变化[J].中山大学学报医学科学版,2006,27(3):266-270.
[98]于淼,朴春丽,南征,等.2型糖尿病胰岛素抵抗的肝内炎症发病机制与毒损肝络病机制论的相关性探讨[J].中国中西医结合杂志,2006,26(11):1032.