摘要
本论文分为糖尿病的理论探讨和临床研究两个部分。
第一部分理论探讨
本论文的理论探讨从祖国医学的角度,对糖尿病的认识、病因病机、辨证论治体系进行了阐述。
第二部分临床研究
目的研究需使用胰岛素治疗的2型糖尿病(T2DM)患者加用参芪复方后胰岛β细胞功能是否有一定的改善,同时观察它对氧化应激及血GLP-1等的影响以探讨参芪复方可能的作用机制。
对象及方法单用胰岛素治疗的2型糖尿病患者随机分为试验组和对照组,试验组使用胰岛素和参芪复方,对照组单用胰岛素,研究期为12周。于基线和研究结束时分别进行口服葡萄糖耐量试验(OGTT)+C肽释放试验(100g标准馒头餐),测量血糖、C肽、GLP-1(均为0小时、0.5小时、2小时)；HbAlc;空腹胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白一胆固醇(HDL-c).低密度脂蛋白一胆固醇(LDL-c).游离脂肪酸(NEFA).总的超氧化物歧化酶(T-SOD).丙二醛(MDA)、可溶性E-选择素(sE-selectin)、可溶性血管细胞黏附分子-1(sVCAM-1)；疑血酶原时间(PT)、活化部分凝血活酶时间(APTT)纤维蛋白原(Fib)、血红蛋白、肝肾功等。△CP30/△G30评估早相C肽的分泌。计算HOMA-β、HOMA-IR以分别反映胰岛β细胞功能和胰岛素抵抗。
结果42位患者进入研究,40位完成研究。基线时,两组患者的一般资料及观测指标经过统计学分析均无统计学差异(p>0.05),研究结束时,试验组临床总疗效、中医症状、体征积分均优于对照组。无论是试验组还是对照组的各点的血糖均有明显降低,HbAlc亦有明显降低分别为[(10.97±1.23vs7.71±1.01)%,p<0.05]。试验组试验后与试验前相比0.5hC肽[(0.86±0.42vs1.59±0.54)nmol/L,p=0.000],△CP30/△G30(0.07±0.48vs0.53±0.51,p=0.01)均明显升高,对照组无明显变化；试验组试验后与对照组试验后相比0.5hC肽[(1.22±0.43vs1.59±0.54)nmol/L,p=0.023],△CP30/△G30(0.27±0.22vs0.53±0.51,p=0.04),表明试验组试验后0.5hC肽、△CP30/△G30与对照组相比改善明显且差异有统计学意义。试验组与试验前相比0hGLP-1[(219.88±100.14vs266.17±105.63)pg/mL,p=0.000],0.5hGLP-1[(260.67±104.25vs333.94±114.48)pg/mL,p=0.000],2hGLP-1[(211.21±91.85vs245.91±113.32)pg/mL,p=0.001]有升高且差异有统计学意义,对照组无明显变化。试验组试验后与对照组试验后相比OhGLP-1[(227.02±100.15vs266.17±105.63)pg/mL, p=0.315],差异无统计学意义；0.5hGLP-1[(245.98±101.48vs333.94±114.48)pg/mL, p=0.014],差异有统计学意义；2hGLP-1[(211.53±97.08vs245.91±113.32)pg/mL, p=0.309]差异无统计学意义。试验组T-SOD明显升高、MDA. sE-select in、sVCAM-1明显下降。PT.APTT.Fib对照组试验前后无统计学差异,试验组试验前后差异有统计学意义,且试验组试验后与对照组试验后相比差异有统计学意义。试验组的TG.LDL-C均有下降。HDL-c无明显变化,NEFA明显降低[(242.85±252.21vs566.80±476.33)ng/mL,p=0.000],对照组的血脂无明显变化。HOMA-β、HOMA-IR无论是试验组还是对照组差异均无统计学意义。
结论单使用胰岛素控制血糖的T2DM患者,通过12周的参芪复方的治疗可以明显改善这些患者的中医症状及体征、减轻体重、控制血糖、提高HbAlc的达标率、改善β细胞的分泌功能。这些作用部分与参芪复方能够使胰岛素抵抗减轻、脂代谢紊乱改善、凝血功能改善、餐后GLP-1分泌尤其是早相GLP-1增加、氧化应激减少、抗氧化作用提高及血管内皮功能改善有关。
There are two parts in this paper.One part is reference review of diabetes,The other part is clinical research on the treatment for Shenqi Compound Extract combined with insulin therapy in type2diabetic patients.
Reference review
In reference review part of this paper, from the perspective of traditional Chinese medicine, the understanding of diabetes, etiology and pathogenesis, syndrome differentiation and treatment system are described.
clinical research
Objective:To investigate the effects of Shenqi Compound Extract combined with insulin therapy on islet B cell function,especially on early phase of insulin secretion, oxidative stress and on the secretion of glucagon-like peptide-1(GLP-1)in type2diabetic patients who need to use insulin therapy to control bloodglucose.
Methods:Type2diabetic patients who need to use insulin therapy were selected. One is study group and the other is control group. The study group injected insulin and combined with Shenqi Compound Extract orally, the control group only used insulin.This study lasted for12weeks. At baseline and the end of the study,Oral glucose tolerance test(100g standards bread)+C-peptide release test was performed,respectively. Other indices such as plasma glucose,C-peptide,serum GLP-1(0h,0.5h,2h),and HbA1c,total cholesterol(TC),triglycerides(TG), high density lipoprotein cholesterol(HDL-ch) and low density lipoprotein cholesterol(LDL-ch),none stesterified fatty acid (NEFA),total superoxide dismutase(T-SOD),malondialdehyde(MDA),soluble E-selectin (sE-selectin),soluble vascular cell adhesion molecule-1(sVC AM-1),prothrombin time(PT),activated partial thromboplastin (APTT),fibrinogen(Fib),hemoglobin,liver and kidney function were detected. Use ΔCP30/ΔG30to evaluate the early phase of βcell function. Calculated HOMA-β, HOMA-IR to reflect the pancreatic beta cell function and insulin resistance(IR).
Results:Fourty two patients were included in the study and fourty patients finished follow-up. At baseline, the two groups of patients with general information and observations through the statistical analysis were not statistically different (p>0.05).Either the study group or the control group of each point plasma glucose significantly decreased, HbAlc is also significantly decreased[(10.97±1.23vs7.71±1.01)%, p<0.05].After the study, compared with before the study,0.5hC-p of the study group increased[(0.86±0.42vs1.59±0.54)nmol/L,p=0.000] significantly Δ CP30/Δ G30of the study group increased (0.07±0.48vs0.53±0.51,p=0.01) significantly,too.In the control group these indices did not change significantly.0hGLP-1,0.5hGLP-1,2hGLP-1of the study group increased all. T-SOD activity of the study group were improved. Other indices of the study group,such as MDA levels,sE-selectin,sVCAM-1,TG、LDL-C were decreased significantly. NEFA decreased[(242.85±252.21vs566.80±476.33)ng/mL,p=0.000]too. No significant changes in the lipids of the control group. The level of PT,APTT of the study group had shorter than that of the control group. The level of Plasma TG,LDL-C,Fib of the study group were decreased. No significant changes in HDL-c.HOMA-B,HOMA-IR, regardless of the study group or the control group showed no significant difference.
Conclusion:Single-use insulin to control blood sugar in type2diabetic patients,12weeks Shenqi Shenqi Compound Extract treatment can significantly improve the clinical symptoms and signs of these patients, control blood glucose,improve HbAlc compliance rate, improve Bcell function.Effects of Shenqi Compound Extract on these function in type2diabetic patients may relate to the improvement of IR,improvement of lipid metaboli-sm disorders, improvement of Coagulation function,increasing of postprandial GLP-1secretion, especially in the early phase of GLP-1secretion,decreasing in oxidative stress,improvement of the anti-oxidation, improvement of endothelial function.
引文
[1]Yang Wen ying. Prevalenee of Diabetes among Men and Women in China. N Eng 1 J Med,2010,362:1090.
[2]中国2型糖尿病防治指南[M]第1版.北京：中华医学会糖尿病学分会,2011.
[3]Barillari G.Fabbro E,Pasca S,Bigotto E.Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population [J].Blood Coagul Fibrinolysis,2009,20:290-296.
[4]Purreloaf,raabuazza AM.Metabolic fators that affect beta-cell functioan and survival[J].Diabet Nutr Metab,2000,13(2):84-91.
[5]Sivitz WI,Lipotoxicity and glucotoxicity in type 2 diabetes.Effects on development and progression[J].Postgrad Med,2001,109(1):55-64.
[6]Ceriello A, Motz E. Isoxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease?The common soil hypothesis revisited[J]. Arterioscler Thromb Vasc Biol,2004,24(5):816-823.
[7]Asnat BD, Nava B.Proposed mechanisms for the induction of insulin resistance by oxidative stress[J].Antioxid Redox Signal,2005,7(11/12):1553-1567.
[8]Fridlyand LE, Philipson LH.Reactive species and early manifestation of insulin resistance in type2 diabetes[J].Diabetes Obes Metab,2006,8:136-145.
[9]Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes[J].Science,2005,307:384-387.
[10]赵庆斌,王惠芳,孙超峰等.短期胰岛素泵强化治疗对初诊2型糖尿病患者胰岛功能的影响及其氧化应激机制[J].南方医科大学学报,2007,27(12)：1878-1883.
[11]孟柳.2型糖尿病周围神经病变与血清TAOC\MDA\SOD的相关性研究[D]。新疆：新疆医科大学,2008.
[12]Nair N,Bedwal S,Prasad S,et al.Short term zinc deficiency in diet induces increased oxidative stress in tests and epididymis of rats[J].Indian J exp Biol,2005,43(9):786-794.
[13]Bannan S, Mansfield MW, Grant PJ. Soluble vascular cell adhesion molecule-1 and E-selection levels in relation to vascular risk factors and to E-selection genotype in the first degree relatires of NIDDM patients and in NIDDM patients, Diabetologla, 1998,41(4):460.
[14]Hingorani AD,Cross J.Kharbanda RK.et al.Acute systemic inflammation impairs endothelium-dependent dilatation in humans.Circulationg.2000,102:994-999.
[15]Sibai B,Dekker G, Kupferminc M.Preeclampsia[J].Lancet,2005,365 (9461):785-799.
[16]James B. Meigs, Frank B. Hu, Nader Rifai,et al. Biomarkers of Endothelial Dysfunction and Risk of Type 2 Diabetes Mellitus[J].JAMA (Chinese Edition),2005,24(3):138-146.
[17]Dehne MG, Sablotzki A, Muhling J, et al. Evaluation of sE—Selec—tin and slCAM-1 as parameters for renal function[J]. Ren Fail,2008,30(7):675-684.
[18]Hajilooi M, Sanati A, Ahmadieh A. Circulating ICAM-1,VCAM-1, E-selectin,P-selectin, and TNFRII in patients with coronaryartery disease[J].Immunol Invest,2004,33(3):263-275.
[19]Armstrong EJ, Morrow DA, Sabatine MS.Inflammatory biomarkers in acutecoronary syndromes:part Ⅱ:acute phase reactants and biomarkers of endothelial cell activation [J].Circulation,2006,113(1):152-155.
[20]Matsumoto K,Sera Y,NakamuraH,et al.Serum concentrations of soluble adhesion molecules are related to degree of hyperglycem ia and insulin resistance in patients Pract, with type 2 diabetes mellitus [J]. Diabetes Res Clin,2002,55(2):131-138.
[21]Yang XD, Sara AM, Reina EM, et al. The role of cell adhesion molecules in the development of IDDM[J]. Diabetes,2003,45(6):705-710.
[22]邢玉波.粘附分子与糖尿病[J].国外医学：内分泌学分册,2001,21(1)：6-8.
[23]Elrick H. Plasma insulin response to oral and intravenous glucose administration[J].J Clin Invest,1964,24:1076-1082.
[24]Perlely MJ,Kipnis DM.Plasma insulin responses to oral and intravenous glucose studies:studies in normal and diabetes subjects[J].J Clin Invest,1967,46:1954-1962.
[25]卞爱琳,陈东升.胰高血糖素样肽1及其类似物的研究进展[J].2011,17 (8)：1195-1196.
[26]Valverde I, Wang GS, Burghardt K, et al.Bioactive GLP-1 in gut, receptor expression in pancreas,and insulin response to GLP-1 in diabetes prone ras[J]. Endocrine,2004,23:77-84.
[27]Li Y, Hansotia T, Yusta B, et al.Glucagon-like-peptide-1 receptor signaling modulates βcell apoptosis[J].Biol Chem,2003,278(7):471-478.
[28]Hongbin Liu, Yunshan Hu,Richard W S. Glucagon-like peptide-1 attenuates tumour necrosis factor-a-mediated induction of glucagon-like peptide-1 activator inhibitor-1 expression[J]. Clin Endocrinol Metab,2008,196(2):57-65.
[29]Perry, Harold W, Ananda,et al.Evidence of GLP-1-mediated neuroprotection in animal model of pyridoxine-induced peripheral sensory neuropathy[J].Exp Neurol,2007,203(2):293-301.
[30]Leiter LA, Lewanczuk RZ. Of the renin—angiotensin system and reactive oxygen species type 2 diabetes and angiotensin Il inhibition[J]. Am J Hypertens,2005,18(1):121-128.
[31]张海燕.《黄帝内经》对消渴病的认识[J].中华中医药学刊,2007,25(6)：1239-1241.
[32]高中祖.<内经)论消渴[J].云南中医学院学报,2000,23(4)：44-47.
[33]张介宾.景岳全书[M].上海：上海科学技术出版社,1959：9.
[34]王学华.消渴病古今名家验案全析[M].北京：北京科学技术文献出版社,2004：120-122.
[35]张锡纯.医学衷中参西录[M].石家庄：河北人民出版社,1977：156-159.
[36]董建华.中国现代名中医医案精华[M].北京：北京人民卫生出版社,2010：165-167.
[37]李冀,王春丽.消渴从心辨治论[J].中医药学报,2000,1：3-5.
[38]郑筱萸.中药新药临床研究指导原则(试行)[M],北京：中国医药科技出版社,2002：233-234.
[39]糖尿病及其并发症中西医诊治学[M].北京：人民卫生出版社,1997,238-243.
[40]黄佳娜.糖尿病从气阴两虚论治的理论探讨[J].中国中医基础医学杂 志,2000,6(9)：561-562.
[41]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)：10917-1918.
[42]岳仁宋,龚光明,李一北.糖尿病中医证治思路探讨[J].中国中医药信息杂志,2008,15(10)：85-86.
[43]王晓南.从痰、湿、热、虚、瘀论治糖尿病[J].光明中医,2010,25(7)：1273-1274.
[44]马晖,谢春光.参芪复方降血糖实验研究[J].四川省卫生管理干部学院学报,2006,25(2)：87-89.
[45]王芬,何华亮,张红敏.参芪复方对GK大鼠脂代谢异常的实验研究[J].天津中医药,2007,24(6)：507-508.
[46]谢毅强,谢春光,张红敏.参芪复方对GK大鼠早期动脉硬化胰岛素抵抗的影响[J].海南医学院学报,2007,13(3)：204-207.
[47]张红敏,陈世伟,谢春光.参芪复方对GK大鼠炎症标志物的影响及机理探讨[J].中药材,2006,29(3)：249-253.
[48]张红敏,陈世伟,谢春光.参芪复方对GK大鼠白色脂肪组织脂联素基因表达的影响[J].中成药,2006,28(7)：996-1001.
[49]陈敏,高泓,谢春光.参芪复方对GK大鼠主动脉COX2mRNA表达影响的实验研究[J].中华中医药杂志,2010, (09)：1456-1461.
[50]谢毅强,谢春光,张红敏.参芪复方对GK大鼠2型糖尿病大血管病变CD36mRNA及OX-LDL的影响[J].时珍国医国药,2001,18(8)：1812-1814.
[51]张红敏,谢春光,陈世伟.参芪复方对糖尿病早期大血管病变大鼠白色脂肪过氧化酶体增殖物激活受体γ的影响[J].中医杂志,2007,48(6)：549-551,562.
[52]陈敏,庄灿,谢春光.参芪复方对GK大鼠大血管病变内皮细胞凋亡影响的实验研究[J].时珍国医国药,2010,21(9)：2165-2166.
[53]康健,刘桠,谢春光.参芪复方对GK大鼠心肌细胞凋亡相关因子Bcl-2、Bax及NO的影响[J].天津中医药,2009,26(6)：489-490.
[54]高泓,谢春光,刘桠.参芪复方对糖尿病大血管病变GK大鼠PI3K/AKT信号通路的影响[J].中医杂志,2011,1：49-54.
[55]刘桠,谢春光,陈敏.参芪复方调控GK大鼠血管PTEN/PI3K通路的实验研究[J].中国中西医结合杂志,2010,30(6)：640-644.
[56]谢毅强,李军茹,张红敏.参芪复方治疗2型糖尿病胰岛素抵抗的临床研究[J].中华实用中西医杂志,2005,18(17)：844-846.
[57]马萍,胡荣,王小英等.中药人参治疗糖尿病的研究进展[J].湖北中医药大学学报,2013,15(1)：63-65.
[58]李世辉.人参皂甙RgI对2型糖尿病患者高凝状态作用的临床观察[J].中华实用中西医杂志,2004,4(17)：702-703.
[59]李冬方,何小丽,都基莎,等.黄芪多糖心血管药理作用研究概况[J].辽宁中医杂志,2013,40(3)：586-587.
[60]高美风,黄容,陈云芳.黄芪多糖的提取及其治疗糖尿病药理作用进展[J].辽宁中医药大学学报,2008,10(6)：38-40.
[61]孙晓生,谢波.山药药理作用的研究进展[J].中药新药与临床药理[J].2011,22(3)：353-355.
[62]何云,戚玉敏,刘景升,等.山药多糖对糖尿病大鼠胰岛素及血小板数的影响[J].河北北方学院学报(医学版),2009,26(1)：29-31.
[63]刘软华,朱红丽.山茱萸的现代药理研究及应用[J].中国医药指南.2012,10(31)：601-603.
[64]刘洪,许惠琴,时艳.山茱萸环烯醚萜总苷对2型糖尿病心脏病变大鼠胰岛素抵抗及血脂含量的影响[J].中药药理与临床,2007,23(3)：36-40.
[65]时艳,许惠琴.山茱萸环烯醚萜总苷对实验性糖尿病心脏病变的保护作用[Jj.南京中医药大学学报,2006,22(1)：35-37.
[66]刘斌,许惠琴,吴诚等.生地-山茱萸对糖尿病大鼠血管的保护作用[J].中国老年学杂志,2012,32(7)：2750-2752.
[67]孟庆宇,吕秀芳,金秀东.地黄水提液对2型糖尿病大鼠proinsulin基因表达的影响[J].中药材,2008,31(3)：397-399.
[68]吕秀芳,孟庆宇,郭新民.地黄水提液对2型糖尿病大鼠胰岛素抵抗及resistin基因mRNA和蛋白表达的影响[J].中国中药杂志,2007,32(20)：2182-2184.
[69]赵润生,张一听,苗冬雪,等.生地黄对血瘀模型大鼠血液流变性的影响[J]. 中药药理与临床,2006,22(3)123.
[70]迟诚,金苗苗,母义明,等.大黄酸上调糖尿病大鼠脂肪组织PPAR-γ及GluT-4表达并改善胰岛素敏感性[J].中国糖尿病杂志2008,16(12)：746-748.
[71]王苑铭,田林红,张娟.大黄多糖对糖尿病动脉粥样硬化大鼠血糖、血脂、肝脂酶活性的影响[J].中国现代医药杂志,2008,10(4)：6-10.
[72]田风胜,李振彬,王元松,等.大黄对糖尿病大鼠血管病变保护机制的研究[J].中国中药杂志,2008,33(6)：673-677.
[73]余传隆.中药辞海[M].北京：中国医药出版社,1993,711.
[74]王听.丹参酮药理研究及临床应用进展[J].光明中医,2011,26(7)：1514-1517.
[75]李博,朱平先,吴清华.丹参酮心血管药理作用及临床应用进展[J].江西医学院学报.2009,49(6)：126-128,132.
[76]贾伟平,项坤三.胰岛β细胞功能评估——从基础到临床[J].中华内分泌代谢杂志,2005,21(3)：199-201.
[77]Bonora E, Targher G, Alberiche M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessmet of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity[J]. Diabetes care,2000,23 (1):57-63.
[78]Menon V,Ram M.Dorn J,et al.Oxidative stress and glucose levels in a population-based sample[J].Diabet Med,2004,21(12):1346-1352.
[79]蒙广星,袁强,王毅军,等.糖尿病大鼠肝脏β-defensins表达及血清炎症因子的变化[J].第四军医大学学报,2009,30(7)：591-594.
[80]殷松楼,周冬梅,奚珏,等.2型糖尿病患者氧化应激指标的变化[J].徐州医学院学报,2010,30(1)：63-64.
[81]Signorini A M, FondelliC, Renzoni E, et al. Antioxidant effects of gliclazide, glibenclamide and metformin in Patients with type 2 diabetes mellitus[J]. J Current Theraputie Res,2002,63(7):411.
[82]蔡林刚,任为.细胞黏附分子血浆E-选择素水平与下肢深静脉血栓形成[J].中国组织工程研究与临床康复,2008,12(46)：9049-9052.
[83]Brosnan CF,Cannella B, Battbtini L, et al.Cytokine localization in multiple sclerosis lesions:correlation with adhesion molecule expression and reactive nitrogen species[J].Neurology,2005,45(suppl 6):S1-S21.
[84]Taubes G. Cardiovascular disease. Does in Flammarion cut to the heart of the matter[J]. Science,2002,296(5566):242-245.
[85]牛小燕,朱本辛.E-选择素与糖尿病视网膜病变[J].国外医学内分泌学分册,2002,22(1)：16-19.
[86]Huppertz B, Kingdom J C. Apoptosis in the trophoblast role of apoptosis in placental morphogenesis [J].J Soc Gynecol Investig,2004,11(6):353-362.
[87]Hui H, Nourparvar A,Zhao X,et al.Glucagon-like peptide-1 inhibits cell apoptosis of insulin-secreting cells via a cyclic 5-adenosine monophosphate-dependent protein kinase A and a phosphatidylinositol 3-kinase-dependent pathway[J].Endocrinology,2003,144:1444-1445.
[88]K.ieffer,Mclntosh,C.H.S,Pederson R.A.Degradation of glucose-dependent Insulinotropicpoly peptide and truncated glucagon-like peptide 1 in vitro and in vitro by dipeptidylpeptidase IV[J].Endocrinology,1995,136:3585-3596.
[89]Zander M, Madsbad S, Madsen JL,et al. Effect of 6-weeks course of glucagons-like peptide 1 on glycemic control,insulin sensitivity,andbeta-cell function in type 2 diabetes:A parallel-group study[J].Lancet,2002,359:824-830.
[90]Salomon B, Lcnschow DJ. Rhee L, et al. B7/CD28costimulation is essential for the homeostasis of the CD24+CD25+immunoregulatory T cells that control auto immune diabetes[J].Immunity,2000,121 (9):431-440.
[91]Valverde I, Wang GS, Burghardt K, et al. Bioactive GLP-1 in gut,recepteor expression inpancreas, and insulin response to GLP-1 in diabetesprone ras[J].Endocrine,2004,23:77-84.
[92]Hongbin Liu, Yunshan Hu, Richard WS. Glucagon-like peptide-1 attenuates tumour necrosis factor-a-mediated induction of plasmogen activator inhibitor-1 expression[J].Clin Endocrinol Metab,2008,196(2):57-65.
[93]YamadaT.Sato A,Nishimori T,et al. Importanece of hypercoagul ability over hyperplycemia for vascular complication in type 2 diabetes[J].Diabetes Res Clin Pract,2000,49(1):23-31.
[94]穆志静,王立.2型糖尿病患者凝血状态研究[J].疑难病杂志,2013；12(1)：26-29.
[95]胡怡,陈思娇,李红燕,等.超重及肥胖对2型糖尿病患者凝血功能及代谢指标的影响研究[J].中国全科医学,2011,12(14)：478-481.
[96]Lewis G F, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogen esis of insulin resistance and type 2 diabetes[J].Endocr Rev,2002,23:201-229.
[1]李方莲,杜玉君,王棉等.卷柏对老龄糖尿病模型鼠的降血糖作用[J].中国老年学杂志,1999,19(9)：301-302.
[2]施红,金国琴,高尤亮,等.石斛合剂对衰老糖尿病大鼠胰腺组织凋亡相关基因Bax,Bcl-2mRNA及蛋白表达的调控[J].中国老年学杂志,2006,1(26)：57-60.
[3]朱德增,魏晓,赵莉,等.酸味中药复方对2型糖尿病大鼠细胞凋亡及相关基因表达的影响[J].中药新药与临床药理。2006,1(17)：21-24.]
[4]宋福印,栗德林,周景华等.消渴停对胰岛B细胞凋亡及相关基因Bcl-2、Fas蛋白表达的影响[J].中国中医药信息杂志,2001 8(6)：24-26.
[5]刘倩,白素芬,王慧芳等,参芪麦地颗粒对糖尿病大鼠降血糖作用的研究[J].时珍国医国药,2011,22(10)2434-2436.
[6]毛先睛,欧阳静萍,吴勇.中药黄芪多糖对糖尿病大鼠心肌GLUT4表达的影响[J].武汉大学学报(医学版),2005,4(26)：457-459.
[7]刘竹青,张克良,麻风华.葛根煎剂对糖尿病大鼠降血糖机理的研究[J].中医药信息,2006,3(23)：56-58.
[8]史红莉,朱撸星,钟学礼,等.在非胰岛素依赖型糖尿病中优降糖和中草药CMH疗效评价对比[J].上海医学,1993,16(7)：375—377.
[9]张炜.益气养阴方治疗2型糖尿病的疗效观察[J].河北中医,2002,24(5)：326.
[10]王楠,冯凭.金芪降糖片治疗初诊2型糖尿病患者的疗效观察[J].天津医科大学学报,2008,14(3)：291-293.
[11]王颜刚,许凤,陈新焰等.复方中药生芪降糖颗粒对糖尿病大鼠血清生化指标影响的量效关系[J].中国临床康复,2006：10(35)75-76.
[12]郝贤,王星云,姜德友.健脾活血方对2型糖尿病大鼠胰岛素抵抗的影响[J].中医药学报,2009,37(4)：18.
[13]郝贤,付雪艳,马艳春.健脾活血法对2型糖尿病大鼠胰腺组织形态学的影响[J].时珍国医国药,2011,22(.4)：1007-1008.
[14]尚炽昌,李建生.芪蓉降糖冲剂治疗非胰岛素依赖型糖尿病临床观察[J].河南中医,1998,5(25)：132-135.
[15]陈淑英,李育浩,吴清和等.五子衍宗丸对链脉佐菌素所致糖尿病大鼠的影 响[J].新中医,1992,11：52-54.
[16]张冰,高云艳,江佩芬,等.菊苣胶囊对小鼠血糖水平的影响[J].北京中医药大学学报.1999,22(1)：28-30.
[17]谢海林,朱路佳,陆群,等.消渴平降血糖作用研究[J].中成药,1996,18(10)：28.
[18]王黎霞,施顺清.治疗2型糖尿病中药制剂的研究进展[J].中草药,2003,34(12)：9.
[19]许扬,刘春丽,刘彪,WX-JT复方降血糖作用研究[J].中国实验方剂学杂志,2012：18(12)161-165.
[20]陶枫,朱蕴华,姚政,等.健脾清化方对糖尿病模型大鼠GLP-1表达的影响[C].首届国际中西医结合内分泌代谢病学术大会暨糖尿病论坛论文集,2008：664-668.
[21]陶枫,姚政,陆灏,等.健胰方影响2型糖尿病患者肠促胰岛素GLP-1表达的临床观察[J].中药应用,2007,18(12)：934-936.
[22]余文珍,施红,郑燕芳.石斛合剂对衰老糖尿病大鼠血清GLP-1水平的影响[J].海南医学院学报,2006,12(3)：196-199.
[23]李艳君,武艳丽,云长海,等.消渴汤方剂对2型糖尿病大鼠GLP-1分泌的影响[J].解剖科学进展,2005,11(1)：43-44,48.
[24]张红敏,陈世伟,谢春光,等.参芪复方抗自发性糖尿病GK大鼠早期动脉粥样硬化的作用机制[J].中国中药杂志2006,31(15)：1272.
[25]陈敏,庄灿,谢春光,等.参芪复方对GK大鼠大血管病变内皮细胞凋亡影响的实验研究[J].时珍国医国药2010,21(9)：2165-2166.
[26]Leslie SJ, Rahman MQ, Denvir MA, et al. Endothelins and their inhibition in the human skin microcirculation:ET(1-31), a new vasoconstrictor peptide[J]. British Journal of Clinical Pharmacology.2004,57(6):720-725.
[27]Li B, Yao J, Morioka T.Nitric.oxide increases albumin permeability of isolated rat glomeruli via a phosphorylation.dependent mechanism [J]. J Am Soc Nephrol, 2004,12:2116-2624.
[28]张兰,朱志强,牛西武等.中药复方对糖尿病大鼠血浆内皮素、血清一氧化氮 的影响[J].中国中医药信息杂志,2006,13(10)：30-31.
[28]粱晓春,崔丽英,郭赛珊,等.筋脉通治疗糖尿病周围神经病变的临床观察[J].中国中西医结合杂志,1999,19(9)：517-519.
[30]张克俭,粱晓春,崔丽英,等.筋脉通胶囊对糖尿病周围神经病变患者钠.钾.腺苷三磷酸酶活性的影响[J].中医杂志,2001,42(3)：159-161.
[31]梁晓春,都伟欣,贾力,等.桂辛通对糖尿病大鼠山梨醇及神经传导速度的影响[J].中国中药杂志,1999,24(12)：749—751.
[32]燕小霞.大黄糖肾胶囊治疗早期糖尿病肾病疗效观察[J].辽宁中医杂志,2001,28(1)：33.
[33]杨竞,李淑玲,杨进,等.糖神散治疗2型糖尿病周围神经病变临床研究[J].山东中医杂志,2001,20(4)：201.204.
[34]陈信义.通脉胶囊对糖尿病足血液流变性及甲襞徽循环的影响[J].中国微循环,2000,4(2)：113-114.
[35]蔡炳勤,郭智涛,王建春.祛腐生肌膏促进糖尿病足溃痔愈合作用的临床研究[J].中国中医药信息杂志,2000,7(8)：49-50.
[36]张红红,潘秉余.参地生津胶囊治疗气阴两虚兼血瘀型2型糖尿病临床疗效及对血液流变学的影响[J].河北中医,2009,31(6)：827-828,897.
[37]草和欣,何立群.糖肾宁对早期糖尿病肾病大鼠肾脏高滤过的影响[J].上海中医杂志,2001,5：19-21.
[38]宫伟星,徐国安.糖肾通宝饮对早期糖尿病肾病及液流变学改善作用的临床观察[J].新中医,2002,34(1)：30-32.
[39]徐郁杰,张庆怡,陆敏,等.黄芪对糖尿病大鼠肾皮质TGF-α表达的影响.中华内分泌代谢杂志.1998,14(5)：312—314.
[40]Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease?The common soil hypothesis revisited[J]. Arterioscler Thromb Vasc Biol,2004,24(5):816-823.
[41]Whight E Jr,Scism—Bacon JL.Oxidative stress in type 2 diabetes:the role of fasting and postprandial glycaemia[J]. Int J Clin Pract,2006,60(3):308-314.
[42]蔡薇薇,王友群,寇红云。不同中药复方降糖作用机制研究. 中国医药导报,2010,7(22)：31-33,35.
[43]宋惠丽,田风胜,乔萍,等.三黄片对糖尿病便秘患者内皮素一1及一氧化氮的影响[J].中国中医药科技,2010,17(4)：285—286.
[44]田风胜,王芳玲,李华君等.三黄片对糖尿病患者血清超氧化物歧化酶及丙二醛的影响[J].中国中医药信息杂志,2012,1(19)：16-18.
[45]李建英.糖尿病肾病与核因子一KB信号通路[J].山东医药,2010,50(1)：110.
[46]孙凤平,谢春光,殷丽平等.参芪复方对糖尿病肾病GK大鼠肾核转录因子KB的影响[J].时珍国医国药,2011,22(10)：2467-2468.
[47]刘建军,喇万英,王慧芳等,复方黄芪颗粒对糖尿病大鼠糖脂代谢及胰岛功能的影响[J].时珍国医国药,2011,22(8)：1923-1926.
[48]王平,马芳玲,母义明,等.2型糖尿病伴高甘油三酯血症患者血清胰岛素样生长因子结合蛋白1水平与胰岛素抵抗的相关性分析[J].中国糖尿病杂志,2007,15(3)：140.
[49]周亚兵.罗若茵,赵莉酸味中药复方对实验性2型糖尿病大鼠胰岛素抵抗的影响.中国中西医结合杂志.2005,25(5)：441-444.
[50]唐代屹.郭赛珊,孙仁宇.仙贞片对糖尿病大鼠肾皮质终末期糖化终产物及其受体mRNA表达的影响.中国中西医结合杂志,2005,25(1)：60—63.
[51]Tominaga M. Kimura M. Sugiyama K. et al. Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotoein—induced diabetic rats. Diabetes Res Clin Pract 1995; 29 (1):11-17.
[52]张振贤,朱良争,钟家宝,等.调脂降糖片治疗糖尿病血瘀证30例疗效观察.中国中西医结合杂志.2006,26(1)：72—74.
[53]李旋珠,熊洪艳,林青.强胰降糖胶囊对糖尿病模型夫鼠的影响.中国中西医结合杂志,2005,25(121)：1109-1111.
[54]苏文弟,张柏林.中药糖复康胶囊对2型糖尿病患者脂质代谢紊乱的影响[J].天津中医学院学报,2000,19(2)：30—31.
[55]邓晓明,韩崇旭,李继成,等.糖脉宁防治糖尿病血管并发症的实验研究[J].中国中医基础医学杂志,2001,7(4)：39—41.
[56]牛瑾玉,蒋红心,陈宏如,等.平脂合剂对糖尿病脂代谢紊乱及血液流变学的影响[J].新中医,2000,32(12)：37—38.
[57]冯兴中,周镇苏,陈岚,等.消糖片治疗气阴两虚痰瘀互阻型型糖尿病的临床观察[J].北京中医药大学学报,1999,22(5)：41.42.