脉络宁及葛根素注射液联用对2型糖尿病小鼠脑损伤相关因子表达的影响
|
摘要
糖尿病是严重危害人类健康的常见病,已成为仅次于肿瘤和心血管疾病之后的第三大疾病。糖尿病由于体内存在胰岛素抵抗和(或)胰岛素分泌不足,使糖和脂代谢发生紊乱,极易发生大血管和微血管病变,并给大脑带来一系列损害,应引起高度重视。常见2型糖尿病对大脑的损害主要表现为脑血管疾病(主要包括血栓性脑梗死、脑栓塞、短暂性脑缺血发作、腔隙性脑梗死以及出血性脑卒中)和糖尿病性脑病(由于糖尿病糖代谢紊乱导致脑血管改变,损害了中枢神经系统,使大脑在结构、神经生理及神经精神等方面发生病理改变,以获得性认知行为缺陷为特征的糖尿病慢性并发症)。中医药对2型糖尿病脑损伤的防治作用,已被临床认可并广泛使用。深入探讨中医药对2型糖尿病脑并发症的作用机理对于指导临床有着重要意义。脉络宁注射液和葛根注射液在临床常用于2型糖尿病并发症的治疗,对于改善高血糖、高血脂,预防控制微血管和大血管并发症等均有较好疗效,本实验通过观察两药合用的干预作用,旨在探讨脉络宁注射液和葛根素注射液联用防治糖尿病脑损伤的作用机制。
1.文献研究:就中医对糖尿病脑损伤的认识;中药治疗糖尿病脑损伤的研究进展;现代医学对于糖尿病脑损伤的发病机制、相关研究方法、以及KKAy小鼠动物模型建立等方面进行了总结和综述。
2.实验研究:
目的:研究脉络宁注射液与葛根素注射液联用治疗糖尿病小鼠脑损伤可能的作用机制。探讨从中医“毒损脑络”理论出发,利用益气养阴、通络化瘀中药治疗糖尿病脑损伤的作用机制。
方法:①将2型糖尿病模型KKAy小鼠分为模型组和治疗组。同龄C57BL/J小鼠作为正常组。治疗组小鼠14周龄开始以腹腔注射的方式给药。隔周测定各组小鼠的体重和血糖,并分别于20、24和28周龄处死小鼠取血,检测生化指标,同时取小鼠脑组织观察其病理形态变化。②采用免疫组化化学法,检测小鼠脑组织中ICAM-1和Caspase-3的表达。③采用酶联免疫吸附法(ELISA)方法,检测小鼠血清中sICAM-1和sE-selectin含量。
结果:①KKAy小鼠14周龄以后出现了明显的肥胖、倦怠、多尿、高血糖;20周以后出现高脂血症;28周出现脑组织形态学改变;脉络宁注射液与葛根素注射液联用治疗后,治疗组体重增长减缓,血糖降低,血脂受到控制,KKAy小鼠脑组织病理改变减轻。②KKAy小鼠脑组织中ICAM-1和Caspase-3表达增多。脉络宁注射液与葛根素注射液联用治疗后,表达有所降低。③KKAy小鼠血清中sICAM-1含量显著增加, sE-selectin含量无改变。
结论:①脉络宁注射液与葛根素注射液联用可以改善KKAy小鼠的体重、高血糖、高血脂,减轻脑组织的病理损伤。②脉络宁注射液与葛根素注射液联用可以减少粘附分子ICAM-1的表达及血清中含量。同时可以减少Caspase-3的表达。这种对血管内皮细胞的粘附分子ICAM-1及凋亡级联反应中关键因子Caspase-3的控制作用,可能是两种中药抗糖尿病脑损伤的作用机理。
Diabetes mellitus (DM) is a common disease that seriously hurts people's health. And it is regarded as the third leading cause of death following tumor and cardiovascular disease.Diabetic mellitus makes the Lipid and glucose metabolic disorder , that is highly susceptible to macrovascular and microvascular diseases. Diabetic mellitus is caused by Insulin Resistance and absolutely or relatively absence of insulin so that affects the brain. Above all, it is necessary to pay attention to the harm of Diabetic mellitus.The injury of the brain which is affected by Type 2 diabetes mellitus is cerebrovascular disease and diabetic encephalopathy.Traditional Chinese Medicine control for Brain Injury of type 2 diabetes mellitus is approved by clinics and widely used.To further study the curative effect of Chinese medicine in treating complication of type 2 diabetes mellitus has great importance to the clinical guidance.Mailuoning injection combines Puerarin injection was used to treat complication of type 2 diabetes mellitus in clinic , they can reduce hyperglycemia, hyperlipemia and control the macrovascular and microvascular diseases. We combine the Mailuoning injection combines Puerarin injection to investigate the mechanism of control for Brain Injury of diabetes mellitus.
1.Literature research:According to the Chinese medicine to diabete’s understanding,the Chinese medicine treats diabetes’research development:The modern medicine the pathogenesis which damages to diabetes and related technique, KKAy mice animal model’s aspects and so on establishment,carry on the summary and the review.
2.Experiment research:Objective:Investigate the mechanism of Mailuoning injection combines Puerarin injection to treat Brain Injury of diabetes mellitus. Discuss the specific mechanism of Chinese medicine which supplementing qi and nourishing yin、removing blood stasis and activating collaterals in treatment of Brain Injury of diabetes mellitus.
Methods:①KKAy mice were randomly divided into two groups: model and treatment group. C57BL/J mice were used to be controls. Treatment group were given by peritoneal from fourteen weeks old. Weight and fasting plasma-glucose were measured fortnightly. They were sacrificed at 20, 24 and 28weeks of age respectively. Serum creatinine, urea, lipids were measured, the changes of the pathomorphology was also be observed.②ICAM-1 and Caspase-3 were detected in cerebral of mice tissue by immunohisto-chemical method.③sICAM-1 and E-selectin were detected in blood of mice tissue by ELISA method.
Results:①KKAy mice developed obesity, hyperglycemia after 14 weeks age; developed hyperlipemia at 20 weeks of age; developed the changes of the pathomorphology at 28 weeks of age. After the treatment of Mailuoning injection combines Puerarin injection, the weight of KKAy mice was declined, the hyperglycemia was declined and the hyperlipemia was controlled, the changes of the pathomorphology was also declined.②The expression of ICAM-1 and Caspase-3 in brain of KKAy mice were upregulated. while after the treatment of the Mailuoning injection combines Puerarin injection, the expression was inhibited.③The content of sICAM-1 in blood of KKAy mice was increased, and the content of sE-selectin was invariable.
Conclusion:①Mailuoning injection combines Puerarin injection improved weight, hyperglycemia, hyperlipemia and reduce the pathology damage of brain.②Mailuoning injection combines Puerarin injection inhibited the expression of ICAM-1 and Caspase-3. The control action of ICAM-1 -the vascular endothelial cells adhesion molecule and apoptosis cascades reaction’s key effector Caspase-3 maybe the mechanism of control for Brain Injury of diabetes mellitus.
1.文献研究:就中医对糖尿病脑损伤的认识;中药治疗糖尿病脑损伤的研究进展;现代医学对于糖尿病脑损伤的发病机制、相关研究方法、以及KKAy小鼠动物模型建立等方面进行了总结和综述。
2.实验研究:
目的:研究脉络宁注射液与葛根素注射液联用治疗糖尿病小鼠脑损伤可能的作用机制。探讨从中医“毒损脑络”理论出发,利用益气养阴、通络化瘀中药治疗糖尿病脑损伤的作用机制。
方法:①将2型糖尿病模型KKAy小鼠分为模型组和治疗组。同龄C57BL/J小鼠作为正常组。治疗组小鼠14周龄开始以腹腔注射的方式给药。隔周测定各组小鼠的体重和血糖,并分别于20、24和28周龄处死小鼠取血,检测生化指标,同时取小鼠脑组织观察其病理形态变化。②采用免疫组化化学法,检测小鼠脑组织中ICAM-1和Caspase-3的表达。③采用酶联免疫吸附法(ELISA)方法,检测小鼠血清中sICAM-1和sE-selectin含量。
结果:①KKAy小鼠14周龄以后出现了明显的肥胖、倦怠、多尿、高血糖;20周以后出现高脂血症;28周出现脑组织形态学改变;脉络宁注射液与葛根素注射液联用治疗后,治疗组体重增长减缓,血糖降低,血脂受到控制,KKAy小鼠脑组织病理改变减轻。②KKAy小鼠脑组织中ICAM-1和Caspase-3表达增多。脉络宁注射液与葛根素注射液联用治疗后,表达有所降低。③KKAy小鼠血清中sICAM-1含量显著增加, sE-selectin含量无改变。
结论:①脉络宁注射液与葛根素注射液联用可以改善KKAy小鼠的体重、高血糖、高血脂,减轻脑组织的病理损伤。②脉络宁注射液与葛根素注射液联用可以减少粘附分子ICAM-1的表达及血清中含量。同时可以减少Caspase-3的表达。这种对血管内皮细胞的粘附分子ICAM-1及凋亡级联反应中关键因子Caspase-3的控制作用,可能是两种中药抗糖尿病脑损伤的作用机理。
Diabetes mellitus (DM) is a common disease that seriously hurts people's health. And it is regarded as the third leading cause of death following tumor and cardiovascular disease.Diabetic mellitus makes the Lipid and glucose metabolic disorder , that is highly susceptible to macrovascular and microvascular diseases. Diabetic mellitus is caused by Insulin Resistance and absolutely or relatively absence of insulin so that affects the brain. Above all, it is necessary to pay attention to the harm of Diabetic mellitus.The injury of the brain which is affected by Type 2 diabetes mellitus is cerebrovascular disease and diabetic encephalopathy.Traditional Chinese Medicine control for Brain Injury of type 2 diabetes mellitus is approved by clinics and widely used.To further study the curative effect of Chinese medicine in treating complication of type 2 diabetes mellitus has great importance to the clinical guidance.Mailuoning injection combines Puerarin injection was used to treat complication of type 2 diabetes mellitus in clinic , they can reduce hyperglycemia, hyperlipemia and control the macrovascular and microvascular diseases. We combine the Mailuoning injection combines Puerarin injection to investigate the mechanism of control for Brain Injury of diabetes mellitus.
1.Literature research:According to the Chinese medicine to diabete’s understanding,the Chinese medicine treats diabetes’research development:The modern medicine the pathogenesis which damages to diabetes and related technique, KKAy mice animal model’s aspects and so on establishment,carry on the summary and the review.
2.Experiment research:Objective:Investigate the mechanism of Mailuoning injection combines Puerarin injection to treat Brain Injury of diabetes mellitus. Discuss the specific mechanism of Chinese medicine which supplementing qi and nourishing yin、removing blood stasis and activating collaterals in treatment of Brain Injury of diabetes mellitus.
Methods:①KKAy mice were randomly divided into two groups: model and treatment group. C57BL/J mice were used to be controls. Treatment group were given by peritoneal from fourteen weeks old. Weight and fasting plasma-glucose were measured fortnightly. They were sacrificed at 20, 24 and 28weeks of age respectively. Serum creatinine, urea, lipids were measured, the changes of the pathomorphology was also be observed.②ICAM-1 and Caspase-3 were detected in cerebral of mice tissue by immunohisto-chemical method.③sICAM-1 and E-selectin were detected in blood of mice tissue by ELISA method.
Results:①KKAy mice developed obesity, hyperglycemia after 14 weeks age; developed hyperlipemia at 20 weeks of age; developed the changes of the pathomorphology at 28 weeks of age. After the treatment of Mailuoning injection combines Puerarin injection, the weight of KKAy mice was declined, the hyperglycemia was declined and the hyperlipemia was controlled, the changes of the pathomorphology was also declined.②The expression of ICAM-1 and Caspase-3 in brain of KKAy mice were upregulated. while after the treatment of the Mailuoning injection combines Puerarin injection, the expression was inhibited.③The content of sICAM-1 in blood of KKAy mice was increased, and the content of sE-selectin was invariable.
Conclusion:①Mailuoning injection combines Puerarin injection improved weight, hyperglycemia, hyperlipemia and reduce the pathology damage of brain.②Mailuoning injection combines Puerarin injection inhibited the expression of ICAM-1 and Caspase-3. The control action of ICAM-1 -the vascular endothelial cells adhesion molecule and apoptosis cascades reaction’s key effector Caspase-3 maybe the mechanism of control for Brain Injury of diabetes mellitus.
引文
1. 田德禄.中医内科学.北京:中国中医药出版社,2005,718-725.
2. 钱荣立.糖尿病临床指南.北京:北京医科大学出版社,2000,7-12.
3. 赵进喜,王世东,张丽芬.糖尿病相关中医病名考辨.辽宁中医杂志,2005,32(9):889-890.
4. 赵进喜.糖尿病及其并发症中医药防治现状与前景展望.中华中医药杂志,2003,2:1-5.
5. 钱荣立.糖尿病临床指南.北京:北京医科大学出版社,2000,7-12.
6. 赵进喜.浅谈糖尿病的中医病机与辨证论治.陕西中医药研究,1999,4:45-46.
7. 仝小林,胡洁,李洪皎,等.糖尿病的中医治疗.中华中医药杂志,2006,21(6):349-352.
8. 孙万森,吴喜利,杨成志.消渴病病机循证研究.第八次全国中医糖尿病学术大会论文汇编,2005.
9. 陶枫.脾与糖尿病探微.第八次全国中医糖尿病学术大会论文汇编,2005.
10. 谢杜红,仝小林,徐远.糖尿病从肝胃辨治论.中国中医药信息杂志,2003,10(2).
11. 吕仁和,赵进喜,王世东.糖尿病及其并发症的临床研究.新中医杂志,2001,3:3-5.
12. 贾正平.“久病入络”临证应用辨识.实用中医内科杂志,2002,16(2) :71-72.
13. 吴以岭,主编. 络病学.北京:中国科学技术出版社,2004.650-663.
14. 徐灿坤,曹怡玲,谢芳等.从络论治糖尿病慢性并发症.山东中医杂志,2002,21(7) :390-392.
15. 陈宪民.络病初探.山东中医杂志,1998,17(8):341.
16. 徐公富.糖尿病预防展望.医学与哲学,1993,(5):12-14.
17. 冯颖,吴德康.黄连、小檗碱及其复方在抗糖尿病方面的药理学研究及临床应用.中国中医药信息杂志,2003,10(4):80.
18. 朴春梅.黄芪对糖尿病的药理机理研究近况.云南中医中药杂志,2005,26(2):54-6.
19. 杨红,池黠,张蕾.雷氏丹参片对糖尿病患者血脂及高凝状态相关指标的作用.中成药, 2005, 27(12) :附 7-8.
20. 章梅,李旭,邱根全.丹参注射液对Ⅱ型糖尿病患者血小板膜糖蛋白表达的作用.中药材, 2003, 26(10) : 738-9.
21. 陈凤银,叶盛英.桑叶抗糖尿病研究概况.药学实践杂志,2005, 23(2): 71-4.
22. 李卫东,刘先华,周安,等.桑叶提取液对实验性糖尿病大鼠血糖、血脂和蛋白质糖化终末产物的影响.湖北中医学院学报, 2006, 8(2): 36-7.
23. 吴湘英糖尿病的中药疗法研究.World Health Digest,2007,4(11):82.
24. 王洪巨,黄元伟,孙坚,等.通心络胶囊对不稳定型心绞痛患者血管内皮功能的影响.中国中西医结合杂志,2003,23(8):587-589.
25. 徐江平,芮耀诚,李铁军.银杏提取物对培养的脑微血管内皮细胞与单核细胞和中性粒细胞粘附的拮抗作用.中国药理学学报,1999,20(5):423-425.
26. 程云峰.糖尿病并发症防治进展.健康报,1998,2.
27. 潘善余.益肾化痰祛瘀法治疗糖尿病脑病证治探讨. 浙江中医杂志.2006,41(10):594.
28. 王秋红,刘淑霞,凌亦凌.大鼠糖尿病肾病时硝基酪氨酸的表达及葛根素的对抗作用.河北医科大学学报,2004,25(5):263-279.
29. 付荣国,马力群,薛荣亮等.葛根素注射液对大鼠短暂肾却学再灌注损伤的保护作用.中国中西医结合急救杂志,2002,9(4):194.
30. 赵慧娟,罗贵军.葛根素治疗 2 型糖尿病的疗效观察.实用中西医结合临床,2005,5(1):23.
31. 杨沛群,许少辉,陈朝俊.葛根素注射液治疗 2 型糖尿病 41 例临床观察.中医药导报,2006,12(7):16.
32. 韩瑚.葛根素注射液治疗糖尿病 36 例.广州医学院学报,2000,28(3):75-76
33. 段有金,王韶颖,王晓颖等.葛根对蛋白质非酶糖基化的抑制作用.沈阳药科大学学报,2000,17(1):61.
34. Brownlee M,Vlassara H,Cerami A.Nonenzymatic glycosylation and the pathogenesis of diabetic complication.Ann Intern Med,1987,101:527.
35. 朱国行.脑梗塞的溶栓治疗.国外医学(神经外科分册),1995,22(2):5.
36. 敬满芳,于俊琪.葛根素配脉络宁注射液治疗脑梗死 30 例.中国中医急症,2006,15(8):862.
37. 戴克敏,袁昌齐,归信谊,等.常用中药的药理及应用.南京:江苏科学技术出版社,1981,258.
1. 高鑫.糖尿病血管病变的机制.中华中医学杂志,2005,85(35):2 457-2 458.
2. Fielding CJ,Have lRJ,Todd KM,etal.Effects of dietarycholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men[J].J Clin Invest,1995,95:611-618.
3. Dedov II,Shestakov MV,Kochemasova TV,et al.Endothelial Dysfunction in the development of ascular complications in iabetes ellitus[J].Ross Fiziol Zh Im IM Sechenova,2001,87(8):1073-1084.
4. Giugliano D,Ceriello A,Paolisso G.Oxidativ stress and diabetic vascular complications[J].Diabetes Care,1996,19:257-267.
5. Bombeli T,Mueller M,Haeberi A.Anticoagulant properties of the vascular endothelium[J].Thromb Haemost,1997,77:408-423.
6. Dai J,Vrensen GF,Schlingemann RO.Blood-brain barrier integrity is unaltered In unaltered in human bain cortex with diabetes mellitus.Brain Res,2002,954:311.
7. Bouchard P,Ghitescu LD,Bendayan M.Morpho-functional studies of blood-brain barrier in streptozotocin-induced diabetic rats.Diabetologia,2002,45:1017.
8. Gispen WH , Biessels GJ.Cognition and synaptic plasticity in diabetes mellitus.Trends Neurosci,2000,23:542.
9. Schulingkamp RJ,Pagano TC,Hung D,et al Insulin receptors and Insulin action In the brain:review and clinical implincations.Neurosci Biobehav Rev,2000, 24:855.
10. Murangyi M,Fujioka M,Qingping H,et.Diabetes activates cell death pathway After transient focal cerebral ischemia.Diabetes,2003,52:481.
11. Matsumoto K,Sera Y,Ueki Y,et al.Comparison of serum Concentrations of soluble adhesion molecules in diabe tic microangiopathy and macroangiopathy. Diabet Med 2002;19:822-828.
12. Otsuki M,Hashimoto K,Morimoto Y,et al.Circulating vascular cell adhesion molecule 21(VCAM21) in ather osclerotic NIDDM patients[J]. Diabetes, 1997,46:2096-2101.
13. 王加林,赵亚平,周玮等.2 型糖尿病患者血清 sICAM-1 和 sVCAM-1 检测及其临床意义.免疫学杂志,1999;15:120-121.
14. Cominacini L,Pratta PA,Garbin U,et al.E-selectin Plasma concentration is influenced by glycaemic control in NIDDM patients:possible role of oxidative stress.Diabetologina,1997,40(5):584-589.
15. 邢玉波.黏附分子与糖尿病.国外医学内分泌学分册,2001,21(1):6-8.
16. Kvasnicka J , skrha J , Perusicova J , et al.Haemostasis. cytoadhesive molecules(sE-selectinandsICAM-1) and Inflammatory markers in non-insulin dependent diabetes mellitus (NIDDM).SbLek,1998,99(2):97-101.
17. Tailor A,Grange rDN.Role of adhesion molecules in vascular regulation and damage.Curr Hypertens Rep,2000,2(1):78-83.
18. Baumgartner parzer S M,wagner L,petterman M,et al.modulation by high glucose of adhesion molecule expression in cultured endothelial cells[J].Diabetologia,1995,38:1357-1370.
19. KawamuraT,Umemura T,Kanai A,et al.The incidence and charater is ticsof silent cerebral infarctioninel derly diabet inpatients:association with serum-soluble adhesion molecule[J].Diabetologia,1998,41:911-917.
20. Rhodes C J.Type 2 diabetes a matter of beta cell life and death? Science,2005,307:380-384.
21. Conrad CH,Brooks WW,Hayes JA,et al.My ocardialfibros is an stiffness with hypertrophy and heart failure in the spontaneously pertensive rat. Circulation .1995,91:161~170
22. 王艳荣,钱荣立,马小伟,等.实验性糖尿病大鼠肝糖尿合成酶活性改变.北京医科大学学报,1998,30(2):46-48.
23. Chinnaiyan AM,Orourke K,Lane BR,et al.Interaction of CED-4 withCED-3 and CED-9 :a molecular frame work for cell death .Science,1997,21;275(5303):1122-1126.
24. Reddy S,Bradley J,Ginn S,et al.Immunohistochemical study of caspase-3 expressing cells within the pancreas of non-obese diabetic mice during Cyclophosphamide-accelerated diabetes.Histochem CellBiol, 2003, 119:451 -461.
25. Liadis N,Murakami K,Eweida I,et al.Caspase-3 dependent beta -cell apoptosis in the initiation of autoimmune diabetes mellitus.Mol Cell Biol,2005,25:3620-3629.
1. 赵咏梅,徐 纯,张 岱..小鼠糖尿病脑病神经元退变的机制及β淀粉样蛋白前体17 肽的作用.中华内分泌代谢杂志,2000;16:246-9.
2. UK Propective Diabetes Study Group. Intensive blood glucose control with sulphony lureasorin sulin compared with conventional treatment and risk of complication sinpatients with type 2diabetes(UKPDS33).Lancet,1998,352:837-853.
3. ReavenGM,ThomPsonIW,Hahum Detal Relation ship between hyperglyeemia and eognitive funetion inolder NIDDM patients.Diabetes Care,1990,13:16.
4. 许曼音,陆广华,陈名道,等.糖尿病学.上海科学技术出版社,2003:181-214·
5. 徐公富.糖尿病预防展望.医学与哲学,1993,(5):12-14.
6. 李澎涛,王永炎,黄启福.“毒损脑络”病机假说的形成及其理论与实践意义[J],北京中医药大学学报,2001,24(1):1-6+16.
7. 冯学功,刘茂才,黄培新,等.中风病毒邪界定与治疗初探[J].中国中医药信息杂志,2001,8(6):3-5.
1. Yang X D,Sytwu H K,McDevitt H O,et al.Involvement of be-ta7 integrin and mucosal address in cell adhesion molecule-1 (Mad CAM-1) in the development of diabetes in non obese diabetic mice[J].Diabetes,1997,46:1542-1547.
2. 邢玉波.粘附分子与糖尿病.国外医学内分泌学分册,2001,21(1):6-8.
3. Matsumoto K,Sera Y,Ueki Y,etal.Comparison of serum concentrations of soluble adhesion molecules in diabetic micro angiopathy and macro angiopathy.Diabet Med 2002;19:822-828.
4. 王加林,赵亚平,周玮,等.Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1检测及其临床意义.免疫学杂志 1999;15:120-121.
5. Bose K,Clark A C.Dimeric procaspase-3 unfolds via afour-state equilib-rium process.Biochemistry,2001,40:14236-14242.
6. Chai J,Wu Q,Shiozaki E,et al.Crystal structure of aprocaspase-7z mogen:mechanism of activation and substrate binding. Cell ,2001 , 107:399-407.
1. Kvasnicka J,Skrha J,Perusicova J,et al.Haemostasis,cytoadhesive molecules (sE-selectin and sICAM-1)and inflame matory markers in non-insulin dependent diabetes mellitus(NIDDM).SbLek,1998,99:97-101.
2. 邢玉波.粘附分子与糖尿病.国外医学内分泌学分册,2001,21:6-8.
3. Lim SC,Caballero AE,Smakowski P,et al.Soluble intercellular adhe-sion molecule,vascular cell adhesion molecule,and impaired micrivas-cular reactivity are earl markers of vasculopathy in type 2diabetic individuals without microallbuminuria.Diabetes Care,1999,22:1865-1870.
4. Cominacini L,Fratta PA,Garbin U,et al.E-selectin plasma concentration is influenced by glycaemic control in NIDDM patients:possible role of oxidative stress.Diabetologia,1997,40:584-589.
5. 姜文宇.粘附分子与糖尿病慢性并发症.国外医学内科学分1999,26:294-296.
2. 钱荣立.糖尿病临床指南.北京:北京医科大学出版社,2000,7-12.
3. 赵进喜,王世东,张丽芬.糖尿病相关中医病名考辨.辽宁中医杂志,2005,32(9):889-890.
4. 赵进喜.糖尿病及其并发症中医药防治现状与前景展望.中华中医药杂志,2003,2:1-5.
5. 钱荣立.糖尿病临床指南.北京:北京医科大学出版社,2000,7-12.
6. 赵进喜.浅谈糖尿病的中医病机与辨证论治.陕西中医药研究,1999,4:45-46.
7. 仝小林,胡洁,李洪皎,等.糖尿病的中医治疗.中华中医药杂志,2006,21(6):349-352.
8. 孙万森,吴喜利,杨成志.消渴病病机循证研究.第八次全国中医糖尿病学术大会论文汇编,2005.
9. 陶枫.脾与糖尿病探微.第八次全国中医糖尿病学术大会论文汇编,2005.
10. 谢杜红,仝小林,徐远.糖尿病从肝胃辨治论.中国中医药信息杂志,2003,10(2).
11. 吕仁和,赵进喜,王世东.糖尿病及其并发症的临床研究.新中医杂志,2001,3:3-5.
12. 贾正平.“久病入络”临证应用辨识.实用中医内科杂志,2002,16(2) :71-72.
13. 吴以岭,主编. 络病学.北京:中国科学技术出版社,2004.650-663.
14. 徐灿坤,曹怡玲,谢芳等.从络论治糖尿病慢性并发症.山东中医杂志,2002,21(7) :390-392.
15. 陈宪民.络病初探.山东中医杂志,1998,17(8):341.
16. 徐公富.糖尿病预防展望.医学与哲学,1993,(5):12-14.
17. 冯颖,吴德康.黄连、小檗碱及其复方在抗糖尿病方面的药理学研究及临床应用.中国中医药信息杂志,2003,10(4):80.
18. 朴春梅.黄芪对糖尿病的药理机理研究近况.云南中医中药杂志,2005,26(2):54-6.
19. 杨红,池黠,张蕾.雷氏丹参片对糖尿病患者血脂及高凝状态相关指标的作用.中成药, 2005, 27(12) :附 7-8.
20. 章梅,李旭,邱根全.丹参注射液对Ⅱ型糖尿病患者血小板膜糖蛋白表达的作用.中药材, 2003, 26(10) : 738-9.
21. 陈凤银,叶盛英.桑叶抗糖尿病研究概况.药学实践杂志,2005, 23(2): 71-4.
22. 李卫东,刘先华,周安,等.桑叶提取液对实验性糖尿病大鼠血糖、血脂和蛋白质糖化终末产物的影响.湖北中医学院学报, 2006, 8(2): 36-7.
23. 吴湘英糖尿病的中药疗法研究.World Health Digest,2007,4(11):82.
24. 王洪巨,黄元伟,孙坚,等.通心络胶囊对不稳定型心绞痛患者血管内皮功能的影响.中国中西医结合杂志,2003,23(8):587-589.
25. 徐江平,芮耀诚,李铁军.银杏提取物对培养的脑微血管内皮细胞与单核细胞和中性粒细胞粘附的拮抗作用.中国药理学学报,1999,20(5):423-425.
26. 程云峰.糖尿病并发症防治进展.健康报,1998,2.
27. 潘善余.益肾化痰祛瘀法治疗糖尿病脑病证治探讨. 浙江中医杂志.2006,41(10):594.
28. 王秋红,刘淑霞,凌亦凌.大鼠糖尿病肾病时硝基酪氨酸的表达及葛根素的对抗作用.河北医科大学学报,2004,25(5):263-279.
29. 付荣国,马力群,薛荣亮等.葛根素注射液对大鼠短暂肾却学再灌注损伤的保护作用.中国中西医结合急救杂志,2002,9(4):194.
30. 赵慧娟,罗贵军.葛根素治疗 2 型糖尿病的疗效观察.实用中西医结合临床,2005,5(1):23.
31. 杨沛群,许少辉,陈朝俊.葛根素注射液治疗 2 型糖尿病 41 例临床观察.中医药导报,2006,12(7):16.
32. 韩瑚.葛根素注射液治疗糖尿病 36 例.广州医学院学报,2000,28(3):75-76
33. 段有金,王韶颖,王晓颖等.葛根对蛋白质非酶糖基化的抑制作用.沈阳药科大学学报,2000,17(1):61.
34. Brownlee M,Vlassara H,Cerami A.Nonenzymatic glycosylation and the pathogenesis of diabetic complication.Ann Intern Med,1987,101:527.
35. 朱国行.脑梗塞的溶栓治疗.国外医学(神经外科分册),1995,22(2):5.
36. 敬满芳,于俊琪.葛根素配脉络宁注射液治疗脑梗死 30 例.中国中医急症,2006,15(8):862.
37. 戴克敏,袁昌齐,归信谊,等.常用中药的药理及应用.南京:江苏科学技术出版社,1981,258.
1. 高鑫.糖尿病血管病变的机制.中华中医学杂志,2005,85(35):2 457-2 458.
2. Fielding CJ,Have lRJ,Todd KM,etal.Effects of dietarycholesterol and fat saturation on plasma lipoproteins in an ethnically diverse population of healthy young men[J].J Clin Invest,1995,95:611-618.
3. Dedov II,Shestakov MV,Kochemasova TV,et al.Endothelial Dysfunction in the development of ascular complications in iabetes ellitus[J].Ross Fiziol Zh Im IM Sechenova,2001,87(8):1073-1084.
4. Giugliano D,Ceriello A,Paolisso G.Oxidativ stress and diabetic vascular complications[J].Diabetes Care,1996,19:257-267.
5. Bombeli T,Mueller M,Haeberi A.Anticoagulant properties of the vascular endothelium[J].Thromb Haemost,1997,77:408-423.
6. Dai J,Vrensen GF,Schlingemann RO.Blood-brain barrier integrity is unaltered In unaltered in human bain cortex with diabetes mellitus.Brain Res,2002,954:311.
7. Bouchard P,Ghitescu LD,Bendayan M.Morpho-functional studies of blood-brain barrier in streptozotocin-induced diabetic rats.Diabetologia,2002,45:1017.
8. Gispen WH , Biessels GJ.Cognition and synaptic plasticity in diabetes mellitus.Trends Neurosci,2000,23:542.
9. Schulingkamp RJ,Pagano TC,Hung D,et al Insulin receptors and Insulin action In the brain:review and clinical implincations.Neurosci Biobehav Rev,2000, 24:855.
10. Murangyi M,Fujioka M,Qingping H,et.Diabetes activates cell death pathway After transient focal cerebral ischemia.Diabetes,2003,52:481.
11. Matsumoto K,Sera Y,Ueki Y,et al.Comparison of serum Concentrations of soluble adhesion molecules in diabe tic microangiopathy and macroangiopathy. Diabet Med 2002;19:822-828.
12. Otsuki M,Hashimoto K,Morimoto Y,et al.Circulating vascular cell adhesion molecule 21(VCAM21) in ather osclerotic NIDDM patients[J]. Diabetes, 1997,46:2096-2101.
13. 王加林,赵亚平,周玮等.2 型糖尿病患者血清 sICAM-1 和 sVCAM-1 检测及其临床意义.免疫学杂志,1999;15:120-121.
14. Cominacini L,Pratta PA,Garbin U,et al.E-selectin Plasma concentration is influenced by glycaemic control in NIDDM patients:possible role of oxidative stress.Diabetologina,1997,40(5):584-589.
15. 邢玉波.黏附分子与糖尿病.国外医学内分泌学分册,2001,21(1):6-8.
16. Kvasnicka J , skrha J , Perusicova J , et al.Haemostasis. cytoadhesive molecules(sE-selectinandsICAM-1) and Inflammatory markers in non-insulin dependent diabetes mellitus (NIDDM).SbLek,1998,99(2):97-101.
17. Tailor A,Grange rDN.Role of adhesion molecules in vascular regulation and damage.Curr Hypertens Rep,2000,2(1):78-83.
18. Baumgartner parzer S M,wagner L,petterman M,et al.modulation by high glucose of adhesion molecule expression in cultured endothelial cells[J].Diabetologia,1995,38:1357-1370.
19. KawamuraT,Umemura T,Kanai A,et al.The incidence and charater is ticsof silent cerebral infarctioninel derly diabet inpatients:association with serum-soluble adhesion molecule[J].Diabetologia,1998,41:911-917.
20. Rhodes C J.Type 2 diabetes a matter of beta cell life and death? Science,2005,307:380-384.
21. Conrad CH,Brooks WW,Hayes JA,et al.My ocardialfibros is an stiffness with hypertrophy and heart failure in the spontaneously pertensive rat. Circulation .1995,91:161~170
22. 王艳荣,钱荣立,马小伟,等.实验性糖尿病大鼠肝糖尿合成酶活性改变.北京医科大学学报,1998,30(2):46-48.
23. Chinnaiyan AM,Orourke K,Lane BR,et al.Interaction of CED-4 withCED-3 and CED-9 :a molecular frame work for cell death .Science,1997,21;275(5303):1122-1126.
24. Reddy S,Bradley J,Ginn S,et al.Immunohistochemical study of caspase-3 expressing cells within the pancreas of non-obese diabetic mice during Cyclophosphamide-accelerated diabetes.Histochem CellBiol, 2003, 119:451 -461.
25. Liadis N,Murakami K,Eweida I,et al.Caspase-3 dependent beta -cell apoptosis in the initiation of autoimmune diabetes mellitus.Mol Cell Biol,2005,25:3620-3629.
1. 赵咏梅,徐 纯,张 岱..小鼠糖尿病脑病神经元退变的机制及β淀粉样蛋白前体17 肽的作用.中华内分泌代谢杂志,2000;16:246-9.
2. UK Propective Diabetes Study Group. Intensive blood glucose control with sulphony lureasorin sulin compared with conventional treatment and risk of complication sinpatients with type 2diabetes(UKPDS33).Lancet,1998,352:837-853.
3. ReavenGM,ThomPsonIW,Hahum Detal Relation ship between hyperglyeemia and eognitive funetion inolder NIDDM patients.Diabetes Care,1990,13:16.
4. 许曼音,陆广华,陈名道,等.糖尿病学.上海科学技术出版社,2003:181-214·
5. 徐公富.糖尿病预防展望.医学与哲学,1993,(5):12-14.
6. 李澎涛,王永炎,黄启福.“毒损脑络”病机假说的形成及其理论与实践意义[J],北京中医药大学学报,2001,24(1):1-6+16.
7. 冯学功,刘茂才,黄培新,等.中风病毒邪界定与治疗初探[J].中国中医药信息杂志,2001,8(6):3-5.
1. Yang X D,Sytwu H K,McDevitt H O,et al.Involvement of be-ta7 integrin and mucosal address in cell adhesion molecule-1 (Mad CAM-1) in the development of diabetes in non obese diabetic mice[J].Diabetes,1997,46:1542-1547.
2. 邢玉波.粘附分子与糖尿病.国外医学内分泌学分册,2001,21(1):6-8.
3. Matsumoto K,Sera Y,Ueki Y,etal.Comparison of serum concentrations of soluble adhesion molecules in diabetic micro angiopathy and macro angiopathy.Diabet Med 2002;19:822-828.
4. 王加林,赵亚平,周玮,等.Ⅱ型糖尿病患者血清sICAM-1和sVCAM-1检测及其临床意义.免疫学杂志 1999;15:120-121.
5. Bose K,Clark A C.Dimeric procaspase-3 unfolds via afour-state equilib-rium process.Biochemistry,2001,40:14236-14242.
6. Chai J,Wu Q,Shiozaki E,et al.Crystal structure of aprocaspase-7z mogen:mechanism of activation and substrate binding. Cell ,2001 , 107:399-407.
1. Kvasnicka J,Skrha J,Perusicova J,et al.Haemostasis,cytoadhesive molecules (sE-selectin and sICAM-1)and inflame matory markers in non-insulin dependent diabetes mellitus(NIDDM).SbLek,1998,99:97-101.
2. 邢玉波.粘附分子与糖尿病.国外医学内分泌学分册,2001,21:6-8.
3. Lim SC,Caballero AE,Smakowski P,et al.Soluble intercellular adhe-sion molecule,vascular cell adhesion molecule,and impaired micrivas-cular reactivity are earl markers of vasculopathy in type 2diabetic individuals without microallbuminuria.Diabetes Care,1999,22:1865-1870.
4. Cominacini L,Fratta PA,Garbin U,et al.E-selectin plasma concentration is influenced by glycaemic control in NIDDM patients:possible role of oxidative stress.Diabetologia,1997,40:584-589.
5. 姜文宇.粘附分子与糖尿病慢性并发症.国外医学内科学分1999,26:294-296.