LBP-4a改善胰岛素抵抗及治疗糖尿病肾病作用的研究
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摘要
世界各国糖尿病的发病率均在上升,WHO预计到2010年全世界糖尿病的人数将达到2.21亿,其中90%-95%是非胰岛素依赖型糖尿病(NIDDM)。糖尿病肾病(DN)是NIDDM的一种常见而严重的并发症,也是糖尿病患者致死的重要原因。天然抗糖尿病药物以其毒副作用小和不产生耐药性已引起了人们的高度关注,特别是在发展中国家得到了广泛的发展和利用。枸杞多糖(LBP)是从传统的中草药枸杞子中提取出的活性成分,已经发现LBP具有抗癌、抗氧化和降糖的生物活性。但是,关于其治疗NIDDM胰岛素抵抗(IR)和DN作用机理的研究很少有人报道。
本研究采用水提醇沉法从宁夏枸杞中提取出LBP,并对其进行分离、纯化得主要活性成分LBP-4a。采用高糖高脂饮食结合小剂量腹腔注射链脲佐菌素(STZ)建立NIDDM大鼠模型,并将其分为模型对照组、LBP-4a低、高剂量组和罗格列酮治疗组,同时设立正常对照组。应用单细胞凝胶电泳、免疫组化、反转录PCR、酶联免疫吸附试验、免疫沉淀及Western blot等先进技术,从细胞因子、信号转导等方面对LBP-4a降糖、改善IR及治疗DN的作用机理进行了较为深入系统的研究,获得如下研究结果。
(1)宁夏枸杞经烘干、脱脂、脱色、脱小分子糖、乙醇沉淀、有机溶剂洗涤、聚酰胺色谱柱除蛋白、真空干燥后,得粉末状枸杞粗多糖LBP(2.58士0.14(g/100 g))。用DEAE-Cellulose柱层析,并经NaCl梯度洗脱、透析、冻干等步骤,获得4个枸杞多糖级分LBP-1、LBP-2、LBP-3、LBP-4。采用Sephadex G-200柱层析法对级分LBP-4活性成分进一步分离,获得相应的枸杞多糖亚级分LBP-4a。SDS-PAGE银染显示LBP-4a为单一的一条带,冻干品为白色或略显黄色的絮状固体。LBP-4a的得率为1.07%。
(2)LBP-4a处理4周(w),高剂量组可以明显减轻模型大鼠的体重(P<0.01),并显著降低内脏脂肪含量(P<0.05)和空腹血浆胰岛素水平(P<0.01)。LBP-4a不仅对NIDDM大鼠具有降低血糖、血脂和增加抗氧化性的功能,还具有修复DNA损伤的作用。
(3)病理形态学结果显示,LBP-4a对NIDDM大鼠胰腺、肝脏和肾脏有一定的保护作用。光镜下,LBP-4a能使胰岛数量及胰岛内细胞数量增多。电镜下,LBP-4a高剂量组肝细胞核膜完整、清楚,常、异染色质和糖原颗粒分布均匀,粗面内质网结构完整;线粒体肿胀、空泡化和脂肪滴沉积现象减轻。LBP-4a处理组肾小球滤过膜结构基本完整,足突增粗,但排列整齐;基底膜增厚和系膜细胞增生现象明显改善。
(4)对LBP-4a改善NIDDM大鼠IR的机制研究表明,LBP-4a能使NIDDM大鼠骨骼肌细胞的GLUT4进行转位,且这种作用与增加PKB蛋白磷酸化表达有关。
(5)应用Western blot和免疫沉淀方法检测了LBP-4a对NIDDM大鼠骨骼肌p38MAPK蛋白表达的影响。结果表明,LBP-4a能通过增加NIDDM大鼠骨骼肌p38MAPK的活性,从而影响胰岛素的信号转导通路。
(6)对NIDDM大鼠肾功能及肾脏抗氧化活性进行分析,揭示LBP-4a能改善NIDDM大鼠的肾损伤,并能提高NIDDM大鼠肾脏抗氧化酶的活性。
(7)对改善DN功能机制的研究表明,LBP-4a能使NIDDM大鼠肾组织细胞膜PKC活性显著降低(P<0.01),PPAR-γ蛋白含量和PPAR-γmRNA表达显著增加(P<0.01)。免疫沉淀结果显示,LBP-4a对高糖引起的肾组织p38MAPK活性增加有明显的对抗作用。
本文较系统地研究了枸杞多糖LBP-4a亚级分对NIDDM大鼠IR和DN的治疗作用,并多角度地探讨了其作用机制,为进一步深入开展枸杞作为天然抗糖尿病药物的研究提供了科学的理论依据。
The incidence of diabetes mellitus is rapidly increasing in all parts of the world. The World Health Organization has estimated that diabetes mellitus will affect 221 million people worldwide by 2010, and most cases (90-95%) are non-insulin dependent diabetes mellitus (NIDDM). Diabetic nephropathy (DN) is a common but serious complication of NIDDM, and it is a main cause of death in diabetic patients. Recently, the increasing interest has been attracted for development and utilization of antidiabetic plants due to their less side effects and no-drug-resistance, especially in developing countries. Lycium barbarum polysaccharide (LBP), extracted from the traditional Chinese herb Lycium barbarum, is found to have bioactivities such as anticancer, antioxidant and hypoglycemic activities. However, very little is reported about the effect and mechanism of LBP in treating insulin resistance (IR) and DN in NIDDM
LBP was extracted from Ningxia-Lycium barbarum by water extraction and ethanol precipitation technique. And the ingredient of LBP-4a was obtained by separation and purification. The animal model of NIDDM was made by feeding high-glucose and high-fat diet and subjecting to.i.p.little-dose streptozotocin (STZ). The rats of NIDDM model were divided into four groups, including model group, LBP-4a low-dose and high-dose groups, rosiglitazone group and normal control group. In order to research the effect of LBP-4a on reducing blood glucose, ameliorating IR and treating DN in NIDDM rats, a lot of techniques were used such as Single Cell Gel Electrophoresis, immunohistochemical staining, ELISA, immunoprecipitation and Western blot et al. We studyed systematically the effect of LBP-4a on IR and DN in NIDDM rats and researched the mechanism from the point of view of cytokine and signal transduction. The main results were as follows.
(1)LBP was extracted by the following procedure: baking, defatting, discoloration, removing small molecular sugar, deposition by ethanol, cleaning by organic solvent, removing protein by Sephadex G-200 column and vacuum drying, and so on. LBP was powder and the extraction rate was 2.58±0.14(g/100 g). Four LBP fractions, LBP-1, LBP-2, LBP-3 and LBP-4, were got by DEAE-Cellulose column with eluent of NaCl、 dialysis and freeze drying respectively. One sub-fraction LBP-4a was got from the corresponding active LBP-4 fractions by Sephadex G-200 column with water as eluent. LBP-4a was identified to be homogeneous by SDS-PAGE, which showed a single band after staining with Ag. LBP-4a was a white or buff cotton-like solid. The extraction rate of LBP-4a was 1.07%.
(2)After LBP-4a (high-dose) treatment for 4 weeks, body weight and the content of visceral fat mass were evidently decreased (P<0.01, P<0.05) and the level of fasting blood insulin was also significantly decreased (P<0.01). LBP-4a had glucose-lowering and lipid-lowering effects on NIDDM rats. Furthermore, LBP-4a had antioxidative function and repairing DNA damage on NIDDM rats.
(3)The morphologic changes suggested that LBP-4a had protective function on pancreas, liver and kidney in NIDDM rats. It showed that the amount of pancreatic islets and cells was increased by light microscope. An electron micrograph of hepatocyte in high-dose LBP-4a treatment rats showed the nuclear membrane was distinct; the disposition of euchromatin, heterochromatin and glycogen particles is uniform. The rough surfaced endoplasmic reticulum appeared normal. The structural changes in mitochondria with severe swelling, extensive vacuolization and lipid droplets were ameliorated associated with LBP-4a. Ultrastructure of glomerulus was observed by electron microscope. The result displayed that the structure of filter membrane was intact and the foot process was thickening, but their arrangement was regularity after LBP-4a treatment Furthermore, LBP-4a could improve the phenomena of hyperplasia of intercapillary cells and thickening of glomerular basement membrane.
(4)In the present study, the effective mechanism of LBP-4a on insulin resistance was investigated in NIDDM rats. It showed that LBP-4a could induce GLUT4 translocation in skeletal muscle of NIDDM rats, and the effect was related to the increase of hyper-phosphorylated PKB.
(5)By Western blot and immunoprecipitation, the expression and activity of p38MAPK were detected in the skeletal muscle of NIDDM rats. It indicated that administration with LBP-4a could enhance the activity of p38MAPK in skeletal muscle of NIDDM rats, and so, LBP-4a affected the insulin signal transduction passageway.
(6)The effect of LBP-4a on renal function and antioxidative activity of kidney was examined in NIDDM rats. LBP-4a significantly ameliorated diabetic renal damage and enhanced the activities of antioxidant enzymes.
(7)The effective mechanism of LBP-4a on DN was investigated. The results indicated that LBP-4a treatment for 4 weeks, the membrane PKC activity was significantly decreased (P<0.01). The expression of PPAR-γmRNA and the content of PPAR-γwere significantly increased in NIDDM rats kidney treated with LBP-4a (P<0.01). By immunoprecipitation, it showed that LBP-4a could confront the increased activity of p38MAPK induced by hyperglycemia in renal tissue.
In this study, the effects of sub-fraction LBP-4a on IR and DN were investigated systematically in NIDDM rats and the action mechanism was discussed from much points of view. It will provide a comprehensive and scientific evidence for development of Lycium barbarum as a suitable natural antidiabetic agent.
本研究采用水提醇沉法从宁夏枸杞中提取出LBP,并对其进行分离、纯化得主要活性成分LBP-4a。采用高糖高脂饮食结合小剂量腹腔注射链脲佐菌素(STZ)建立NIDDM大鼠模型,并将其分为模型对照组、LBP-4a低、高剂量组和罗格列酮治疗组,同时设立正常对照组。应用单细胞凝胶电泳、免疫组化、反转录PCR、酶联免疫吸附试验、免疫沉淀及Western blot等先进技术,从细胞因子、信号转导等方面对LBP-4a降糖、改善IR及治疗DN的作用机理进行了较为深入系统的研究,获得如下研究结果。
(1)宁夏枸杞经烘干、脱脂、脱色、脱小分子糖、乙醇沉淀、有机溶剂洗涤、聚酰胺色谱柱除蛋白、真空干燥后,得粉末状枸杞粗多糖LBP(2.58士0.14(g/100 g))。用DEAE-Cellulose柱层析,并经NaCl梯度洗脱、透析、冻干等步骤,获得4个枸杞多糖级分LBP-1、LBP-2、LBP-3、LBP-4。采用Sephadex G-200柱层析法对级分LBP-4活性成分进一步分离,获得相应的枸杞多糖亚级分LBP-4a。SDS-PAGE银染显示LBP-4a为单一的一条带,冻干品为白色或略显黄色的絮状固体。LBP-4a的得率为1.07%。
(2)LBP-4a处理4周(w),高剂量组可以明显减轻模型大鼠的体重(P<0.01),并显著降低内脏脂肪含量(P<0.05)和空腹血浆胰岛素水平(P<0.01)。LBP-4a不仅对NIDDM大鼠具有降低血糖、血脂和增加抗氧化性的功能,还具有修复DNA损伤的作用。
(3)病理形态学结果显示,LBP-4a对NIDDM大鼠胰腺、肝脏和肾脏有一定的保护作用。光镜下,LBP-4a能使胰岛数量及胰岛内细胞数量增多。电镜下,LBP-4a高剂量组肝细胞核膜完整、清楚,常、异染色质和糖原颗粒分布均匀,粗面内质网结构完整;线粒体肿胀、空泡化和脂肪滴沉积现象减轻。LBP-4a处理组肾小球滤过膜结构基本完整,足突增粗,但排列整齐;基底膜增厚和系膜细胞增生现象明显改善。
(4)对LBP-4a改善NIDDM大鼠IR的机制研究表明,LBP-4a能使NIDDM大鼠骨骼肌细胞的GLUT4进行转位,且这种作用与增加PKB蛋白磷酸化表达有关。
(5)应用Western blot和免疫沉淀方法检测了LBP-4a对NIDDM大鼠骨骼肌p38MAPK蛋白表达的影响。结果表明,LBP-4a能通过增加NIDDM大鼠骨骼肌p38MAPK的活性,从而影响胰岛素的信号转导通路。
(6)对NIDDM大鼠肾功能及肾脏抗氧化活性进行分析,揭示LBP-4a能改善NIDDM大鼠的肾损伤,并能提高NIDDM大鼠肾脏抗氧化酶的活性。
(7)对改善DN功能机制的研究表明,LBP-4a能使NIDDM大鼠肾组织细胞膜PKC活性显著降低(P<0.01),PPAR-γ蛋白含量和PPAR-γmRNA表达显著增加(P<0.01)。免疫沉淀结果显示,LBP-4a对高糖引起的肾组织p38MAPK活性增加有明显的对抗作用。
本文较系统地研究了枸杞多糖LBP-4a亚级分对NIDDM大鼠IR和DN的治疗作用,并多角度地探讨了其作用机制,为进一步深入开展枸杞作为天然抗糖尿病药物的研究提供了科学的理论依据。
The incidence of diabetes mellitus is rapidly increasing in all parts of the world. The World Health Organization has estimated that diabetes mellitus will affect 221 million people worldwide by 2010, and most cases (90-95%) are non-insulin dependent diabetes mellitus (NIDDM). Diabetic nephropathy (DN) is a common but serious complication of NIDDM, and it is a main cause of death in diabetic patients. Recently, the increasing interest has been attracted for development and utilization of antidiabetic plants due to their less side effects and no-drug-resistance, especially in developing countries. Lycium barbarum polysaccharide (LBP), extracted from the traditional Chinese herb Lycium barbarum, is found to have bioactivities such as anticancer, antioxidant and hypoglycemic activities. However, very little is reported about the effect and mechanism of LBP in treating insulin resistance (IR) and DN in NIDDM
LBP was extracted from Ningxia-Lycium barbarum by water extraction and ethanol precipitation technique. And the ingredient of LBP-4a was obtained by separation and purification. The animal model of NIDDM was made by feeding high-glucose and high-fat diet and subjecting to.i.p.little-dose streptozotocin (STZ). The rats of NIDDM model were divided into four groups, including model group, LBP-4a low-dose and high-dose groups, rosiglitazone group and normal control group. In order to research the effect of LBP-4a on reducing blood glucose, ameliorating IR and treating DN in NIDDM rats, a lot of techniques were used such as Single Cell Gel Electrophoresis, immunohistochemical staining, ELISA, immunoprecipitation and Western blot et al. We studyed systematically the effect of LBP-4a on IR and DN in NIDDM rats and researched the mechanism from the point of view of cytokine and signal transduction. The main results were as follows.
(1)LBP was extracted by the following procedure: baking, defatting, discoloration, removing small molecular sugar, deposition by ethanol, cleaning by organic solvent, removing protein by Sephadex G-200 column and vacuum drying, and so on. LBP was powder and the extraction rate was 2.58±0.14(g/100 g). Four LBP fractions, LBP-1, LBP-2, LBP-3 and LBP-4, were got by DEAE-Cellulose column with eluent of NaCl、 dialysis and freeze drying respectively. One sub-fraction LBP-4a was got from the corresponding active LBP-4 fractions by Sephadex G-200 column with water as eluent. LBP-4a was identified to be homogeneous by SDS-PAGE, which showed a single band after staining with Ag. LBP-4a was a white or buff cotton-like solid. The extraction rate of LBP-4a was 1.07%.
(2)After LBP-4a (high-dose) treatment for 4 weeks, body weight and the content of visceral fat mass were evidently decreased (P<0.01, P<0.05) and the level of fasting blood insulin was also significantly decreased (P<0.01). LBP-4a had glucose-lowering and lipid-lowering effects on NIDDM rats. Furthermore, LBP-4a had antioxidative function and repairing DNA damage on NIDDM rats.
(3)The morphologic changes suggested that LBP-4a had protective function on pancreas, liver and kidney in NIDDM rats. It showed that the amount of pancreatic islets and cells was increased by light microscope. An electron micrograph of hepatocyte in high-dose LBP-4a treatment rats showed the nuclear membrane was distinct; the disposition of euchromatin, heterochromatin and glycogen particles is uniform. The rough surfaced endoplasmic reticulum appeared normal. The structural changes in mitochondria with severe swelling, extensive vacuolization and lipid droplets were ameliorated associated with LBP-4a. Ultrastructure of glomerulus was observed by electron microscope. The result displayed that the structure of filter membrane was intact and the foot process was thickening, but their arrangement was regularity after LBP-4a treatment Furthermore, LBP-4a could improve the phenomena of hyperplasia of intercapillary cells and thickening of glomerular basement membrane.
(4)In the present study, the effective mechanism of LBP-4a on insulin resistance was investigated in NIDDM rats. It showed that LBP-4a could induce GLUT4 translocation in skeletal muscle of NIDDM rats, and the effect was related to the increase of hyper-phosphorylated PKB.
(5)By Western blot and immunoprecipitation, the expression and activity of p38MAPK were detected in the skeletal muscle of NIDDM rats. It indicated that administration with LBP-4a could enhance the activity of p38MAPK in skeletal muscle of NIDDM rats, and so, LBP-4a affected the insulin signal transduction passageway.
(6)The effect of LBP-4a on renal function and antioxidative activity of kidney was examined in NIDDM rats. LBP-4a significantly ameliorated diabetic renal damage and enhanced the activities of antioxidant enzymes.
(7)The effective mechanism of LBP-4a on DN was investigated. The results indicated that LBP-4a treatment for 4 weeks, the membrane PKC activity was significantly decreased (P<0.01). The expression of PPAR-γmRNA and the content of PPAR-γwere significantly increased in NIDDM rats kidney treated with LBP-4a (P<0.01). By immunoprecipitation, it showed that LBP-4a could confront the increased activity of p38MAPK induced by hyperglycemia in renal tissue.
In this study, the effects of sub-fraction LBP-4a on IR and DN were investigated systematically in NIDDM rats and the action mechanism was discussed from much points of view. It will provide a comprehensive and scientific evidence for development of Lycium barbarum as a suitable natural antidiabetic agent.
引文
1刘铜华,吕仁和.中医药防治糖尿病及其并发症的作用途径.北京中医药大学学报, 2000, 23(3): 69-71
2吴寿金,李德玉.降血糖植物多糖的研究概况.中草药, 1992, 23(10): 549-554
3谢明智.中药抗糖尿病的药理作用.中国中西医结合杂志, 2001, 21(4): 318-320
4 H. Himsworth. Diabetes mellitus: its Differentiation into Insulin Sensitive and Insulin Insensitive Type. The Lancet, 1936, 18(3): 127-130
5 S. Jeffrey. Diabetes: the Missing Link with Obesity? Nature, 2001, 40(9): 292-293
6 C. Huang, A.C. Thirone, X. Huang, et al. Differential Contribution of IRS-1 vs.IRS-2 to Insulin Signaling and Glucose Uptake in L6myotubes. J Biol Chem, 2005, 280: 19426-19435
7 P.A. Damn, C. Handberg. Insulin Receptor Binding and Tyrosine Kinase Activity in Skeletal Muscle from Normal Pregnant Women and Women with Gestational. Diabete Obstet Gunecol, 1993, 8(2): 159-163
8 E.A. Dyan. Insulin Action during Pregnancy. Diabetes, 1985, 34(9): 380-389
9 J.L. Evans, I.D. Goldfine, B.A. Maddux. Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes. Endocr Rev, 2002, 23(5): 599-622
10 A.A. Osman, J. Hancock, D.G. Hunt. Exercise Training Increases ERK2 Activity in Skeletal Muscle of Obese Zucker Rats. J Appl Physiol, 2001, 90(2): 454-460
11 H.C. Chen, G. Bandyopadhyay, M.P. Sajan. Activation of the ERK Pathway and Atypical Protein Kinase C Isoforms in Exercise and Aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated Glucose Transport. J Biol Chem, 2002, 277(26): 23554-23562
12 C.Y. Christ, D. Hunt, J. Hancock, et al. Exercise Training Improves Muscle Insulin Resistance but not Insulin Receptor Signaling in Obese Zucker Rats. J Appl Physiol, 2002, 92(2): 736-744
13 R.A. Defrono. The Triumvirate:β-cell, Muscle, Liver a Collusion Responsible for NIDDM. Diabetes, 1988, 37(6): 667-687
14 A. Zisman, O.D. Peroni, E.D. Abel. Targeted Disruption of the Glucose Transporter 4 Selectively in Muscle Cause Insulin Resistance and Glucose Intolerance. Nature Med, 2000, 6(8): 924-928
15 J.K. Andrew, C.J. Bailey. Oral Antidiabetic Agents: Current Role in Type 2 Diabetes Mellitus.Drugs, 2005, 65(3): 385-341
16 E.B. Katz, R. Burcelin, T.S. Tsao, et al. The Metabolic Consequences of Altered Glucose Transporter Expression in Transgenic Mice. Mol Med, 1996, 74(5): 639-652
17 R.T. Watson, J. Pessin. Intracellular Organization of Insulin Signaling and GLUT4 Translocation. Recent Prog Horm Res, 2001, 56(6): 175-193
18 J. Maureen, S. Charron, B. Ellen, et al. GLUT4 Gene Regulation and Manipulation. Biol Chem, 1999, 274(7): 3253-3256
19 D. Konrad, P.J. Bilan, Z. Nawaz, et al. Need for GLUT4 Activation to Reach Maximum Effect of Insulin Mediated Glucose Uptake in Brown Adipocytes Isolated from GLUT4myc Expressing Mice. Diabetes, 2002, 5l(9): 2719-2726
20 E. Carvalho, C. Rondinone, U. Smith, et al. Insulin Resistance in Fat Cells from Obese Zucker Rats Evidence for an Impaired Activation and Translocation of Protein Kinase B and Glucose Transporter 4. Mol Cell Biochem, 2000, 20(6): 7-16
21 H. Storguard, X.M. Song, C.B. Jensen, et al. Insulin Signal Transduction in Skeletal Muscle from Glucose-intolerant Relatives with Type 2 Diabetes. Diabetes, 2001, 50(2): 1770-1778
22 C.M. Rondinone, E. Carvalho, C. Wesslau, et al. Impaired Glucose Transport and Protein Kinase B Activation by Insulin,but not Okadaic Acid, in Adipocytes from Subjects with Type 2 Diabetes Mellitus. Disbetologia, 1999, 4(2): 819-825
23 R.T. Watson, J.E. Pessin. Subcellular Compartmentalization and Trafficking of the Insulin Responsive Gucose Transport GLUT4. Exp Cell Res, 2001, 27(1): 75-83
24 U. Smith, E. Carvalho, E. Mosialou, et al. PKB Inhibition Prevents the Stimulatory Effect of Insulin on Glucose Transportand Protein Translocation but not the Antilipolytic Effect in Rat Adipocytes. Biochem Biophys Res Commun, 2000, 26(8): 315-320
25 M. Fasshauer, J. Klein, S. Neurnann, et al. Biochem Biophys Res Commun, 2001, 288(4): 1027-1031
26 P. Plomgaard, P. Keller, C. Keller, et al. TNF-a, but not IL-6, Stimulates Plasminogen Activator Inhibitor-1 Expression in Human Subcutaneous Adipose Tissue. J Appl Physiol, 2005, 98: 2019-2023
27 E. Verrier, L. Wang, C. Wadham, et al. PPARgamma Agonists Ameliorate Endothelial Cell Activation via Inhibition of Diacylglycerol-protein Kinase C Signaling Pathway: Role ofDiacylglycerol Kinase. Circ Res, 2004, 94(14): 1515-1522
28 J. Vamecq, N. Latruffe. Medical Significance of Peroximme Proliferatoractivated Receptors. Lancet, 1999, 354(14): 141-148
29丁世英,申竹芳等. PPAR与胰岛索抵抗. Chinese Pharmacological Bulletin, 2002, 18(3): 241-245
30 J. Rieusset, C. Chambrier, K. Bouzakri, et al. The Expression of the p85 alpha Subunit of Phosphatidylinositol 3-kinase is Induced by Activation of the Peroximme Proliferator-Activated Receptor gamma in Human Adipocytes. Diabetologia, 2001, 44(3): 544-554
31 E.L. Jack, J.K. Hamm, P.F. Pilch, et al. Reconstitution of Insulin-Sensitive Glucose Transport in Fibroblast Requires Expression of both PPAR gamma and C-EBP alpha. J Biol Chem, 1999, 273(15): 7946-7951
32何戎华.糖尿病现代诊疗.南京:江苏科学技术出版社, 2000: 9-21
33 S. Chowdhury, N. Sengupta. Rational Choice of Oral Antihyperglycaemic Agents. J Indian Med Assoc, 2002, 100(3): 174-175
34 A.H. Barnett. Insulin-Sensitizing Agents-Thiazolidinediones (Glitazones). Curr Med Res, 2002, 18(1): 31-39
35梁兴伦,韩明向.胰岛素抵抗模型大鼠的中医证候研究.中国中西医结合杂志, 2001, 21(7): 528-530
36王永炎.肥胖.中医内科学, 1997, 6(3): 337-340
37李忠.植物药成分的糖代谢效应.中草药, 1987, 18(1): 34-37
38贺兴东,钟赣生主编.临床中医药手册.北京:人民卫生出版社, 1996: 330-345
39 C. Konno, K. Sugiyama, M. Kano, et al. Isolation and Hypoglycaemic Activity of PanaxansA, B, C, D and E, Glycans of Panax Ginseng Roots. Planta Med, 1984, 50(5): 434-436
40王倩.神奇的多糖家族.科技信息, 2002, 3(1): 36-43
41王玲,曾卫玲,张才军等. LBP-D与降糖药对糖尿病小鼠模型血糖和免疫功能的影响.云南大学学报, 1999, 21(3): 30-33
42徐梓辉,周世文,黄林清.薏苡仁多糖的分离提取及其降血糖作用的研究.湖南中医学院学报, 2000, 16(6): 163-166
43欧力,孔令义.苦瓜植物蛋白的研究概况.中草药, 2001, 32(10): 949-951
44 S.L. Sitasawad, Y. Shewade, R. Bhonde. Role of Bittergound Fruit Juice in STZ-inducedDiabetes State in Vivo and Vitro. J Ethopharmaced, 2000, 73(1-2): 71-79
45陈卫辉,钱华,王慧中.麦冬多糖对正常和实验性小鼠血糖的影响.中国现代应用药学, 1998, 15(4): 21-22
46陈蔚,刘芳,俞茂华等.黄芪多糖对NOD小鼠I型糖尿病的预防作用.复旦学报(医学科学版), 2001, 28(1): 57-60
47 H.F. Hikino, C. Konno, M. Takahashi. Isolation and Hypoglycemia Activity of Dioscorans A, B, C, D, E, and F: Gllycans of Dioscorea Japonica Rhizophors. Planta Med, 1986, 52(3): 168-171
48熊学敏,石扬,康明等.南瓜多糖降糖有效部位的提取分离及降糖作用的研究.中成药, 2000, 22(8): 563-565
49刘起华,朱礼,李文兰.刺五加主要活性成分化学与药理研究.时珍国医国药, 1999, 10(4): 305-307
50李云政,秦海元,王清华.国内外芦荟应用研究进展.化工进展, 2000, 2(1): 19-22
51 C. Konno, Y. Suzuki, K. Oishi, et al. Isolation and Hypoglycemic Activity of Atractans A, B and C, Glycans of Atractylodes Japonica Rhizomes. Planta Med, 1985, 2(3): 102-106
52陈建国.茶多糖的提取及其药理作用研究概况.中草药, 2000, 31(7):附6-附7
53王庭欣,赵文,蒋东升等.海带多糖对糖尿病小鼠血糖的调节作用.营养学报, 2001, 23(2): 137-139
54左绍远,罗华君,朱振宇.螺旋藻多搪对糖尿病小鼠抗氧化能力的影响.药物生物技术, 2001, 8(1): 36-38
55 P. Absent. Bellidifolin Stimulates Glucose Uptake in Rat Fibroblasts and Ameliorates Hyperglycemic in Streptozotocin-Induced Diabetic Rats. Planta Medica, 1995, 6(15): 402-405
56徐梓辉,周世文,黄林清等.薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响.中国糖尿病杂志, 2002, 10(1): 44-48
57张艺,扬明,孟突丽等.日本研究多糖的新近展.国外医学中医中药分册, 1997, 19(3): 46-48
58徐梓辉,周世文,黄文权等.薏苡仁多糖对实验性糖尿病大鼠红细胞免疫、T淋巴细胞亚群的影响.湖南中医学院学报, 2001, 21(1): 17-19
59左绍远,罗华君,朱振宇.螺旋藻多糖对糖尿病小鼠抗氧化能力的影响.药物生物技术, 2001, 8(1): 36-38
60陈蔚,刘芳,俞茂华等.黄芪多糖对NOD小鼠1型糖尿病的预防作用.复旦学报(医学科学版), 2001, 28(1): 57-60
61王玲,张才军,李维波等.枸杞多糖对2型糖尿病患者T淋巴细胞亚群和细胞因子的调节作用.河北中医, 2001, 23(12): 888-890
62 L. Thorpm. Diabetic Nephropathy: Common Questions. Am Fam Physician, 2005, 72(1): 96-99
63 T. Vaimadridc, R. Kiein, E. Mosss, et al. The Risk of Cardiovascular Disease Mortality Associated with Microalbuminuria and Gross Proteinuria in Persons with Older onset Diabetes Mellitus. Arch Intern Med, 2000, 160(3): 1093-1100
64 R. Revisan, G. Viberti. Genetic Factors in the Development of Diabetic Nephropathy. J Lab Clin Med, 2002, 126(4): 342-346
65邓权.益肾活血法治疗糖尿病肾病62例.浙江中医杂志, 1996, 31(7): 317-320
66焦鹏.益气活血化瘀法治疗早期糖尿病肾病40例.新中医, 2001, 33(11): 34-36
67韩吉淼,徐文清,刘春荣.程益春教授治疗糖尿病肾病的用药经验.中国中医药信息杂志, 2001, 8(8): 72-75
68程汉桥,赵兴兰.中西医结合治疗早期糖尿病肾病23例.中国中西医结合杂志, 1996, 16(6): 364-365
69王长闵,高军,粱桂芳.中西医结合治疗糖尿病肾病肾功能不全.中医药研究, 2000, 16(4): 8-9
70张国山,陆连芬.益肾活血方治疗糖尿病肾病100例临床研究.天津中医, 2000, 17(3): 17-18
71桑岚.猪苓汤治疗糖尿病肾病35例临床报道.河南中医药学刊, 2000, 15(3): 34-35
72王亚敏.中西医结合治疗糖尿病肾病疗效观察.中国中西医结合肾病杂志, 2002, 3(4): 232-234
73周兴磊,冯志刚,张本祥.冬虫夏草治疗糖尿病肾病90例临床分析.临床医学, 2000, 20(1): 56-57
74田云龙.血塞通注射液干预治疗糖尿病肾病的临床观察.中国中西医结合杂志, 2002, 22(10): 753-755
75占永力.中药三七注射液对显性糖尿病肾病并高凝状态的影响.中国中西医结合肾病杂志, 2002, 3(1): 23-26
76王慧芳,马骏,陈国庆等.大黄对早期糖尿病肾病患者肾脏血流动力的影响.铁道医学, 2001, 29(5): 320-321
77王海松,谢春光.益肾糖泰颗粒对糖尿病大鼠肾脏病变的影响.成都中医药大学学报, 2000, 23(1): 49-51
78李怡,张前进,李秋贵等.糖肾胶囊对FFR胰岛素抵抗性与leptin浓度的影响.中国实验方剂学杂志, 2000, 6(1): 25-27
79白善信.慢性肾衰竭的中草药防治研究.中国中西医结合肾病杂志, 2001, 2(4): 246-248
80冯建春,倪青.时氏糖肾胶囊治疗糖尿病肾病的实验研究.中国实验方剂学杂志, 2000, 6(6): 32-36
81李建生.大黄蛰虫丸对老年糖尿病早期肾病TXB3和6-keto-P的影响.辽宁中医杂志, 1998, 25(10): 53-55
82徐蓉娟,李红,唐红等.治糖保肾冲剂治疗早期糖尿病肾病大鼠的实验研究.上海中医药大学学报,加00, l4(4): 47-49
83刘志红,黎磊石.糖尿病肾病发病机理.中华肾脏病杂志, 1999, 15(2): 120-123
84徐向进,吴玉水,冯修高等.槲皮素对糖尿病大鼠肾脏转化生长因子-β(TGF-β)表达的影响.中国糖尿病杂志, 2001, 9(1): 44-48
85廖璞,王淑琴,廖雪松等.银杏叶提取物对糖尿病大鼠肾脏保护作用的实验研究.中国药房, 2000, 11(3): 114-115
86李英,吴文清,张益民等.野黄芪甙原对糖尿病大鼠肾脏蛋白激酶C活性作用的研究.中华肾脏病杂志, 2000, 16(21): 89-92
87倪海祥,罗苏生,邵国民等.刺五加注射液对早期糖尿病肾脏病变及血浆、尿内皮素的影响.中国中西医结合杂志, 2001, 21(2): 105-107
88 A. Doria, J.H. Warram, A.S. Krolewski. Genetic Susceptibility to Nephropathy in Insulin Dependent Diabetes: from Epidemiology to Molecular Genetics. Diabetes/Metabolism Review, 1995, 11(1): 287-290
89 S.T. Azar, P.A. Zalloua, R. Medlej, et al. The Degenotype of the ACE Gene Polymorphism is Association with Diabetic Nephropathy in the Type-1 Diabetics. Endocr Res,2001, 27(2): 99-108
90 G. Wladylaw, K. Dariusz, M.Z. Moczulski, et a1. Role of GLUTl Gene in Susceptibility to Diabetic Nephropathy in Type 2 Diabetes. Kidney Int, 2001, 59(4): 631-636
91 A. Faneui, S. Hadjadj, Y. Gallois, et a1. Polymorphisms of Aldose Reductase Gene and Susceptibility to Retinopathy and Nephropathy in Caucasians with Type 1 Diabetes. Arch MalCoeur Vaiss, 2002, 95(1): 701-708
92 E. Noiri, H. Satoh, J. Taguchi, et a1. Association of eNOS Glu298Asp Polymorphisms with End-stage Renal Disease. Hypertension, 2002, 40(2): 535-540
93 S. Araki, D.K. Moczulski, L. Hanna, et a1. Am E Polymorphisms and the Development of Diabetic Nephropathy in Typel Diabetes: Results of Case-Control and Family-Based Studies. Diabetes, 2000, 49(3): 2190-2195
94 J.F. Moorhead, M.K. Chin, E.J. Nahasm, et al. Lipid Neophrotoxicity in Chronic Progressive Glomerulur and Tubulo-Intestinal Disease. Lancet, 1982, 2(3): 1309-1311
95 K. Zuzaki, S. kobori, M. Ide, et al. Acetyl-low Density Lipoprotein Receptor on Rat Mesangial Cells. Atherosclerosis, 2003, 101(2): 177-182
96 X.Z. Ruan, Z. Varghese, S.H. Powis, et al. Human Mesangial Cells Express Inducible Macrophage Scvenger Receptor: an Ap-1and ets Nidiated Responese. Kidney Int, 2004, 56(suppl71): S163-S166
97 R. Lehmann, E.D. Schleicher. Molecular Mechanism of Diabetic Nephropathy. Clin Chim Acta, 2000, 297(1): 135-144
98肖谦,汪恕萍.多元醇通路与糖尿病慢性并发症的关系研究进展.国外医学内分泌分册, 2001, 21(7): 128-131
99 P.A. Graven. Nitric Oxide Inhibition of Transforming Growth Factor-βand Collagen Synthesis in Mesangial Cells. Diabetes, 1997, 46(2): 871-877
100 B. Erdos, J.A. Snipes, A.W. Miller, et al. Cerebrovascular Dysfunction in Zucker Obese Rats is Mediated by Oxidative Stress and Protein Kinase C. diabetes, 2004, 53(7): 1352-1359
101 L. Brown. Biochemistry and Molecule Cell Biology of Diabetic Complication of Mellitus. Annual Rev Biochem Nature, 2001, 414(4): 813-820
102 E. Tsiani, P. Lekas, I.G. Fantus, et a1. High Glucose Enhanced Activation of Mesangial Cell p38MAPK by ET-1, ANG-2 and Platelet Derived Growth Factor. A J Physiol Endocrinol Metab, 2002, 282(1): E161-El69
103 J.A. Dlugosz, S. Munk, K. Drezgic, et a1.Stretch Induced Mesangial Cell ERKI/ERK2 Activation is Enhanced in High Glucose by Decreased. Dephosphorylation. Am J physiol Rena lPHysiol, 2000, 21(3): F688-F671
104 S.W. Kang, A.S. Gdler, L.A. Page, et al. p38MAPK and MAPK kinase3/6 mRNA and Activities are Increased in Early Diabetic Golmemli. Kidney Int, 2001, 60(2): 543-552
105 W.A. Willian, C.L. Dixon, C. Hebert, et a1. Chronic Exposure of Human Mesangial Cells to High Glucose Environments Activates the p38MAPK Pathway. Kidney lnt, 2001, 60(3): 858-871
93 S. Araki, D.K. Moczulski, L. Hanna, et a1. Am E Polymorphisms and the Development of Diabetic Nephropathy in Typel Diabetes: Results of Case-Control and Family-Based Studies. Diabetes, 2000, 49(3): 2190-2195
94 J.F. Moorhead, M.K. Chin, E.J. Nahasm, et al. Lipid Neophrotoxicity in Chronic Progressive Glomerulur and Tubulo-Intestinal Disease. Lancet, 1982, 2(3): 1309-1311
95 K. Zuzaki, S. kobori, M. Ide, et al. Acetyl-low Density Lipoprotein Receptor on Rat Mesangial Cells. Atherosclerosis, 2003, 101(2): 177-182
96 X.Z. Ruan, Z. Varghese, S.H. Powis, et al. Human Mesangial Cells Express Inducible Macrophage Scvenger Receptor: an Ap-1and ets Nidiated Responese. Kidney Int, 2004, 56(suppl71): S163-S166
97 R. Lehmann, E.D. Schleicher. Molecular Mechanism of Diabetic Nephropathy. Clin Chim Acta, 2000, 297(1): 135-144
98肖谦,汪恕萍.多元醇通路与糖尿病慢性并发症的关系研究进展.国外医学内分泌分册, 2001, 21(7): 128-131
99 P.A. Graven. Nitric Oxide Inhibition of Transforming Growth Factor-βand Collagen Synthesis in Mesangial Cells. Diabetes, 1997, 46(2): 871-877
100 B. Erdos, J.A. Snipes, A.W. Miller, et al. Cerebrovascular Dysfunction in Zucker Obese Rats is Mediated by Oxidative Stress and Protein Kinase C. diabetes, 2004, 53(7): 1352-1359
101 L. Brown. Biochemistry and Molecule Cell Biology of Diabetic Complication of Mellitus. Annual Rev Biochem Nature, 2001, 414(4): 813-820
102 E. Tsiani, P. Lekas, I.G. Fantus, et a1. High Glucose Enhanced Activation of Mesangial Cell p38MAPK by ET-1, ANG-2 and Platelet Derived Growth Factor. A J Physiol Endocrinol Metab, 2002, 282(1): E161-El69
103 J.A. Dlugosz, S. Munk, K. Drezgic, et a1.Stretch Induced Mesangial Cell ERKI/ERK2 Activation is Enhanced in High Glucose by Decreased. Dephosphorylation. Am J physiol Rena lPHysiol, 2000, 21(3): F688-F671
104 S.W. Kang, A.S. Gdler, L.A. Page, et al. p38MAPK and MAPK kinase3/6 mRNA and Activities are Increased in Early Diabetic Golmemli. Kidney Int, 2001, 60(2): 543-552
105 W.A. Willian, C.L. Dixon, C. Hebert, et a1. Chronic Exposure of Human Mesangial Cells to High Glucose Environments Activates the p38MAPK Pathway. Kidney lnt, 2001, 60(3): 858-87114(4): 481-483
119吴先旺.中西医结合治疗糖尿病肾病53例临床观察.江苏中医药, 2005, 26(2): 21-22
120曲红,王德山.枸杞多糖的药理及临床研究概况.山东医药工业, 2002, 21(4): 36-37
121罗琼,李瑾伟,张声华等.枸杞多糖-X组分对糖尿病家兔降血糖的效果.营养学报, 1997, 19(2): 173-177
122罗琼,阎俊,李瑾伟等.枸杞多糖粗品与纯品抗疲劳作用的比较.营养学报, 1999, 21(3): 310-317
123任彬彬,马永萍,沈泳等.宁夏枸杞及甜菜碱H2O2诱发PRC膜脂质过氧化的影响.中国中药杂志, 1995, 20(5): 303-304
124田丽梅,王昊.枸杞多糖的提取分离和其组成研究.中国中药杂志, 2006, 31(19): 1603-1607
125王建华.枸杞多糖的结构与保健功能评价. [武汉华中农业大学博士论文]. 2001: 17-18
126袁振林.枸杞多糖的提取及含量和分子量分布的测定.广东化工, 2003, 2(3): 43-45
127 M.M. Bradford. A rapid and Sensitive Method for the Quantification of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem, 1976, 72(2): 248-254
128张民.枸杞多糖的特性、结构及生物活性评价. [武汉华中农业大学博士论文]. 2003: 25-35
129何进,张声华.枸杞及枸杞多糖研究.食品科学, 1995, 16(2): 14-21
130黄琳娟,林颖,田庚元等.枸杞中免疫活性成分的分离纯化及物理化学性质的研究.药学学报, 1998, 33(7): 512-516
131王玲,李俊,李欣等.枸杞多糖2对辐射损伤小鼠免疫功能恢复的影响.上海免疫学杂志, 1995, 15(4): 209-212
132李晓莉,王斌,刘嘉麟等.枸杞多糖对小鼠耐缺氧效应的研究.华中农业大学学报, 1999, 18(3): 283-285
133戴春芝,文润玲,李为等.枸杞和枸杞多糖与抗衰延寿,老年学杂志, 1994, 14(1): 33-36
134 H. Sakuraba, H. Mizukami. Reduced beta-cell Mass and Expression of Oxidative Stress Related DNA Damage in the Islet of Japanese Type II Diabetic Patients. Diabetologia, 2002, 45(1): 85-96
135 J. Leinonen, T. Lehtimaki. New Biomarker Evidence of Oxidative DNA Damage in Patients with Non-Insulin-Dependent Diabetes Mellitus. FEBS Letters, 1997, 3(1): 150-152
136 Y. Hinokio, S. Suzuki. Oxidative DNA Damage in Diabetes Mellitus:its Association with Diabetic Complications. Diabetologia, 1999, 42(8): 995-998
137中华人民共和国卫生部制定发布.中药新药临床指导原则第一辑. 1993: 215-232
138郭啸华.实验性2型糖尿病大鼠模型的建立.肾脏病与透析肾移植杂志, 2000, 9(4): 351-355
139李光伟,潘孝仁, S.Lillioja等.检测人群胰岛素敏感性的一项新指标.中华内科杂志, 1993, 32(2): 656-660
140项坤三,贾伟平,陆俊茜等.中国上海地区40岁以上成人中肥胖与代谢综合症的关系.中华内科杂志, 2000, 39(2): 224-228
141朱姿英,薛耀明.高甘油三脂血症和2型糖尿病.中国糖尿病杂志, 2003, 13(2): 153-154
142 A.C. Maritim, R.A. Sanders, J.B. Watkins. Diabetes, Oxidative Stress, and Antioxidants: a review J. Biochem. Mol. Toxicol, 2003, 17(1): 24-38
143游捷.糖尿病患者外周血淋巴细胞DNA单链断裂的研究.中华内分泌代谢杂志, 1997, 13(1): 55-57
144 H.O. Adami, W.H. Chow, O. Nyren, et al. Excess Risk of Primary Liver Cancer in Patients with Diabetes Mellitus. J-Nati-Cancer-Inst, 1996, 88(20): 1472-1477
145 T. William. Insulin Resistance: Cellular and Clinical Concepts. Experimental Biology and Medicine, 2001, 226(7): 13-26
146 H.K. Karlsson, J.R. Zierath. Insulin Stimulated Phosphorylation of the AKT Substrate AS160 is Impaired in Skeletal Muscle of Type 2 Diabetic Subjects. Diabetes, 2005, 54(3): 1692-1697
147 L.R. Derek, Z. Yehiel. Recent Advances in Our Understanding of Insulin Action and Insulin Resistance. Diabetes Care, 2001, 24(3): 588-597
148 C. Alvaro, T. Teruel, R. Hernandez. et al. Tumor Necrosis Factor-alpha Produces Insulin Resistance in Skeletal Muscle by Activation of Inhibitor KappaB Kinase in a p38MAPK Dependent Manner. Journal of Biological Chemistry, 2004, 279(3): 17070-17078
149 C. Huang, R. Somwar, N. Patel, et al. Sustained Exposure of L6 Myotubes to High Glucose and Insulin Decreases Insulin Stimulated GLUT4 Translocation but Upregulates GLUT4 Activity. Diabetes, 2002, 51(7): 2090-2097
150 A. Klip, T. Ramlal, A.J. Young, et al. Insulin Induced Translocation of Glucose Transporters in Rat Hindlimb Muscles. FEBS Lett, 1987, 244(10): 224-230
151 A. Marette, C. Atgie, Z. Liu, et al. Differential Regulation of GLUT1 and GLUT4 Glucose Transporters in Skeletal Muscle of a New Model of Type 2 Diabetes. Diabetes, 1993, 42(5): l195-120l
152 L. Maianu, S.R. Keller, W.T. Garvey, et al. Adipocytes Exhibit Abnormal Subcellular Distributionand Translocation of Vescles Containing GLUT4 and Insulin Regulated Amino Peptidase in Type
2 Diabetes Mellitus: Implications Regarding Defects in Vesicle Trafficking. Clin Endocrinol Metab, 2001, 86(6): 5450-5456
153 L.W. Ileen, C. Han, J. Morris, et al. Role of Aktlprotein Kinase B in Metabolism. Trends in Endocrinology and Metabolism, 2002, 13(3): 444-451
154 H .Cho, J. Mu, J.K. Kim, et al. Insulin Resistance and a Diabetes Mellitus-like Syndrome in Mice Lacking the Protein Kinase Akt2/PKB-beta. Science, 2001, 292(1): 1728-1731
155 E.W. Christian, M.D. Lorna, K.L. Melissa, et al. Protein Kinase BlAkt Prevents Fatty Acid-Induced Apoptosis in Pancreatic Cells (INS-1). J Biol Chem, 2002, 277(3): 49676-49684
156 K.V. Kandror. A Long Search for Glut4 Activation. Sci STKE, 2003, 169(9): 5-9
157 K.F. Howlett, K. Sakamoto, M.F. Hirshman, et al. Insulin Signaling after Exercise in Insulin Receptor Substrate-2-Deficient Mice.Diabetes, 2002, 51(2): 479-483
158 J.L. Evans, I.D. Goldfine, B.A. Maddux, et al. Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes. Endocr. Rev, 2002, 23(5): 599-622
159 R. Somwar, S. Koterski, G. Sweeney, et al. A Dominant-Negative p38 MAPK Mutant and Novel Selective Inhibitors of p38MAPK Reduce Insulin-stimulated Glucose Uptake in 3T3-L1 Adipocytes without Affecting GLUT4 Translocation.J Biol Chem, 2002, 277(52): 50386-50395
160 W. Niu, C. Huang, Z. Nawaz, et al. Maturation of the Regulation of GLUT4 Activity by p38 MAPK during L6 Cell Myogenesis. Biol Chem, 2003, 278(20): 17953-17962
161 X. Xi, J. Han, J.Z. Zhang, et al. Stimulation of Glucose Transport by AMP-activated Protein Kinase via Activation of p38 Mitogen-activated Protein Kinase. J Biol Chem, 2001, 276(44): 41029-41034
162 Y. Guan, M.D. Breyer. Peroxisome Proliferator-activated Receptors (PPARs): Novel Therapeutic Targets in Renal Disease. Kidney Int, 2001, 60(1): 14-30
163 M. Brownlee. Biochemistry and Molecular Cell Biology of Diabetic Complications. Nature, 2001, 414(6865): 813-816
164 R.E. Routh, J.H. Johnson, K.J. Mccarthy, et al. Troglitazone Suppresses the Secretion of Type 1 Collagen by Mesangial Cells in Vitro. Kidney Int, 2002, 61(4): 1365-1376
165 J. Floege, C. Alpers, M.W. Burns, et al. Glomerular Cells, Extracellular Matrix Accumulation, and the Development of Glomerulosclerosis in the Remnant kidney. Lab Invest, 1992, 66(5):485-492
166李才主编.疾病模型与实验病理学.吉林大学出版社, 2002: 117-131
167 H.A. Hunjoo, L.E. Hibahl. Reactive Oxygen Species as Glucose Signaling Molecules in Mesangial Cells Cultured under Gigh Glucose. Kindry lnt, 2005, 58(suppl 77): 19-22
168 H. Ha, H.B. Lee. Reactive Oxygen Species as Glucose Signaling Molecules in Mesangial Cells Cultured under High Glucose. Kidney lnt, 2006, 7(Supp1): 19-25
169 F. Zheng, A. Fornoni, S.J. Elhot, et a1. Upregulation of TypeI Collagen by TGF-beta in Mangial Cells is Blocked by PPAR gamma Activation. Am J Physiol Renal Physiol, 2002, 282(4): F639-F643
170 T. Teruel, R. Hernandez, M. Benito, et a1. Rosiglitazone and Retinoic acid Induce Uncoupling Protein-1(UCP-1)in a p38 Mitogen Activated Protein Kinase Dependent Manner in Fetal Primary Brown Adipocytes. J Biol Chem, 2003, 278(1): 263-269
171 N. Sakai, T. Wada, K. Furuichi, et al. Involvement of Extracellular Signal Regulated Kinase and p38 in Human Diabetic Nephropathy. Am J Kidney Dis, 2005, 45(1): 54-65
172 P.C. Chang, T.H. Chen, C.J. Chang, et al. Advanced Glycosylation end Products Induce Inducible Nitric Oxide Synthase (iNOS) Expression via a p38MAPK Dependent Pathway. Kidney Int, 2004, 65(5): 1664-1675
173 H. Fujita, S. Omori, K. Ishikura, et al. ERK and p38 Mediate High Glucose Induced Hypertrophy and TGF-beta Expression in Renal Tubular Cells. Am J Physiol Renal Physiol, 2004, 286(1): F120-F126
174 S.W. Kang, S.C. Adler, J. LaPage, et al. p38 MAPK and MPAK Kinase 3/6 mRNA and Activities are Increased in Early Diabetic Golmeruli. Kidney Int, 2001, 60(2): 543-552
175 S. Kang, R. Natarajan, A. Shahed, et al. Role of 12-lipoxygenase in the Stimulation of p38 Mitogen Activated Protein Kinase and Collagen alpha5 in Experimental Diabetic Nephropathy and in Glucose Stimulated Podocytes. J Am SocN ephrol, 2003, 14(12): 3178-3187
176 C.W. Park, J.H. Kim, J.H. Lee, et al. High Glucose Induced Intercellular Adhesion Molecule-1 (ICAM) Expression through an Osmotic Effect in Rat Mesangial Cells is PKC-NF KB-dependent. Diabetes, 2000, 43(7): 1544-1557
2吴寿金,李德玉.降血糖植物多糖的研究概况.中草药, 1992, 23(10): 549-554
3谢明智.中药抗糖尿病的药理作用.中国中西医结合杂志, 2001, 21(4): 318-320
4 H. Himsworth. Diabetes mellitus: its Differentiation into Insulin Sensitive and Insulin Insensitive Type. The Lancet, 1936, 18(3): 127-130
5 S. Jeffrey. Diabetes: the Missing Link with Obesity? Nature, 2001, 40(9): 292-293
6 C. Huang, A.C. Thirone, X. Huang, et al. Differential Contribution of IRS-1 vs.IRS-2 to Insulin Signaling and Glucose Uptake in L6myotubes. J Biol Chem, 2005, 280: 19426-19435
7 P.A. Damn, C. Handberg. Insulin Receptor Binding and Tyrosine Kinase Activity in Skeletal Muscle from Normal Pregnant Women and Women with Gestational. Diabete Obstet Gunecol, 1993, 8(2): 159-163
8 E.A. Dyan. Insulin Action during Pregnancy. Diabetes, 1985, 34(9): 380-389
9 J.L. Evans, I.D. Goldfine, B.A. Maddux. Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes. Endocr Rev, 2002, 23(5): 599-622
10 A.A. Osman, J. Hancock, D.G. Hunt. Exercise Training Increases ERK2 Activity in Skeletal Muscle of Obese Zucker Rats. J Appl Physiol, 2001, 90(2): 454-460
11 H.C. Chen, G. Bandyopadhyay, M.P. Sajan. Activation of the ERK Pathway and Atypical Protein Kinase C Isoforms in Exercise and Aminoimidazole-4-carboxamide-1-beta-D-riboside (AICAR)-stimulated Glucose Transport. J Biol Chem, 2002, 277(26): 23554-23562
12 C.Y. Christ, D. Hunt, J. Hancock, et al. Exercise Training Improves Muscle Insulin Resistance but not Insulin Receptor Signaling in Obese Zucker Rats. J Appl Physiol, 2002, 92(2): 736-744
13 R.A. Defrono. The Triumvirate:β-cell, Muscle, Liver a Collusion Responsible for NIDDM. Diabetes, 1988, 37(6): 667-687
14 A. Zisman, O.D. Peroni, E.D. Abel. Targeted Disruption of the Glucose Transporter 4 Selectively in Muscle Cause Insulin Resistance and Glucose Intolerance. Nature Med, 2000, 6(8): 924-928
15 J.K. Andrew, C.J. Bailey. Oral Antidiabetic Agents: Current Role in Type 2 Diabetes Mellitus.Drugs, 2005, 65(3): 385-341
16 E.B. Katz, R. Burcelin, T.S. Tsao, et al. The Metabolic Consequences of Altered Glucose Transporter Expression in Transgenic Mice. Mol Med, 1996, 74(5): 639-652
17 R.T. Watson, J. Pessin. Intracellular Organization of Insulin Signaling and GLUT4 Translocation. Recent Prog Horm Res, 2001, 56(6): 175-193
18 J. Maureen, S. Charron, B. Ellen, et al. GLUT4 Gene Regulation and Manipulation. Biol Chem, 1999, 274(7): 3253-3256
19 D. Konrad, P.J. Bilan, Z. Nawaz, et al. Need for GLUT4 Activation to Reach Maximum Effect of Insulin Mediated Glucose Uptake in Brown Adipocytes Isolated from GLUT4myc Expressing Mice. Diabetes, 2002, 5l(9): 2719-2726
20 E. Carvalho, C. Rondinone, U. Smith, et al. Insulin Resistance in Fat Cells from Obese Zucker Rats Evidence for an Impaired Activation and Translocation of Protein Kinase B and Glucose Transporter 4. Mol Cell Biochem, 2000, 20(6): 7-16
21 H. Storguard, X.M. Song, C.B. Jensen, et al. Insulin Signal Transduction in Skeletal Muscle from Glucose-intolerant Relatives with Type 2 Diabetes. Diabetes, 2001, 50(2): 1770-1778
22 C.M. Rondinone, E. Carvalho, C. Wesslau, et al. Impaired Glucose Transport and Protein Kinase B Activation by Insulin,but not Okadaic Acid, in Adipocytes from Subjects with Type 2 Diabetes Mellitus. Disbetologia, 1999, 4(2): 819-825
23 R.T. Watson, J.E. Pessin. Subcellular Compartmentalization and Trafficking of the Insulin Responsive Gucose Transport GLUT4. Exp Cell Res, 2001, 27(1): 75-83
24 U. Smith, E. Carvalho, E. Mosialou, et al. PKB Inhibition Prevents the Stimulatory Effect of Insulin on Glucose Transportand Protein Translocation but not the Antilipolytic Effect in Rat Adipocytes. Biochem Biophys Res Commun, 2000, 26(8): 315-320
25 M. Fasshauer, J. Klein, S. Neurnann, et al. Biochem Biophys Res Commun, 2001, 288(4): 1027-1031
26 P. Plomgaard, P. Keller, C. Keller, et al. TNF-a, but not IL-6, Stimulates Plasminogen Activator Inhibitor-1 Expression in Human Subcutaneous Adipose Tissue. J Appl Physiol, 2005, 98: 2019-2023
27 E. Verrier, L. Wang, C. Wadham, et al. PPARgamma Agonists Ameliorate Endothelial Cell Activation via Inhibition of Diacylglycerol-protein Kinase C Signaling Pathway: Role ofDiacylglycerol Kinase. Circ Res, 2004, 94(14): 1515-1522
28 J. Vamecq, N. Latruffe. Medical Significance of Peroximme Proliferatoractivated Receptors. Lancet, 1999, 354(14): 141-148
29丁世英,申竹芳等. PPAR与胰岛索抵抗. Chinese Pharmacological Bulletin, 2002, 18(3): 241-245
30 J. Rieusset, C. Chambrier, K. Bouzakri, et al. The Expression of the p85 alpha Subunit of Phosphatidylinositol 3-kinase is Induced by Activation of the Peroximme Proliferator-Activated Receptor gamma in Human Adipocytes. Diabetologia, 2001, 44(3): 544-554
31 E.L. Jack, J.K. Hamm, P.F. Pilch, et al. Reconstitution of Insulin-Sensitive Glucose Transport in Fibroblast Requires Expression of both PPAR gamma and C-EBP alpha. J Biol Chem, 1999, 273(15): 7946-7951
32何戎华.糖尿病现代诊疗.南京:江苏科学技术出版社, 2000: 9-21
33 S. Chowdhury, N. Sengupta. Rational Choice of Oral Antihyperglycaemic Agents. J Indian Med Assoc, 2002, 100(3): 174-175
34 A.H. Barnett. Insulin-Sensitizing Agents-Thiazolidinediones (Glitazones). Curr Med Res, 2002, 18(1): 31-39
35梁兴伦,韩明向.胰岛素抵抗模型大鼠的中医证候研究.中国中西医结合杂志, 2001, 21(7): 528-530
36王永炎.肥胖.中医内科学, 1997, 6(3): 337-340
37李忠.植物药成分的糖代谢效应.中草药, 1987, 18(1): 34-37
38贺兴东,钟赣生主编.临床中医药手册.北京:人民卫生出版社, 1996: 330-345
39 C. Konno, K. Sugiyama, M. Kano, et al. Isolation and Hypoglycaemic Activity of PanaxansA, B, C, D and E, Glycans of Panax Ginseng Roots. Planta Med, 1984, 50(5): 434-436
40王倩.神奇的多糖家族.科技信息, 2002, 3(1): 36-43
41王玲,曾卫玲,张才军等. LBP-D与降糖药对糖尿病小鼠模型血糖和免疫功能的影响.云南大学学报, 1999, 21(3): 30-33
42徐梓辉,周世文,黄林清.薏苡仁多糖的分离提取及其降血糖作用的研究.湖南中医学院学报, 2000, 16(6): 163-166
43欧力,孔令义.苦瓜植物蛋白的研究概况.中草药, 2001, 32(10): 949-951
44 S.L. Sitasawad, Y. Shewade, R. Bhonde. Role of Bittergound Fruit Juice in STZ-inducedDiabetes State in Vivo and Vitro. J Ethopharmaced, 2000, 73(1-2): 71-79
45陈卫辉,钱华,王慧中.麦冬多糖对正常和实验性小鼠血糖的影响.中国现代应用药学, 1998, 15(4): 21-22
46陈蔚,刘芳,俞茂华等.黄芪多糖对NOD小鼠I型糖尿病的预防作用.复旦学报(医学科学版), 2001, 28(1): 57-60
47 H.F. Hikino, C. Konno, M. Takahashi. Isolation and Hypoglycemia Activity of Dioscorans A, B, C, D, E, and F: Gllycans of Dioscorea Japonica Rhizophors. Planta Med, 1986, 52(3): 168-171
48熊学敏,石扬,康明等.南瓜多糖降糖有效部位的提取分离及降糖作用的研究.中成药, 2000, 22(8): 563-565
49刘起华,朱礼,李文兰.刺五加主要活性成分化学与药理研究.时珍国医国药, 1999, 10(4): 305-307
50李云政,秦海元,王清华.国内外芦荟应用研究进展.化工进展, 2000, 2(1): 19-22
51 C. Konno, Y. Suzuki, K. Oishi, et al. Isolation and Hypoglycemic Activity of Atractans A, B and C, Glycans of Atractylodes Japonica Rhizomes. Planta Med, 1985, 2(3): 102-106
52陈建国.茶多糖的提取及其药理作用研究概况.中草药, 2000, 31(7):附6-附7
53王庭欣,赵文,蒋东升等.海带多糖对糖尿病小鼠血糖的调节作用.营养学报, 2001, 23(2): 137-139
54左绍远,罗华君,朱振宇.螺旋藻多搪对糖尿病小鼠抗氧化能力的影响.药物生物技术, 2001, 8(1): 36-38
55 P. Absent. Bellidifolin Stimulates Glucose Uptake in Rat Fibroblasts and Ameliorates Hyperglycemic in Streptozotocin-Induced Diabetic Rats. Planta Medica, 1995, 6(15): 402-405
56徐梓辉,周世文,黄林清等.薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响.中国糖尿病杂志, 2002, 10(1): 44-48
57张艺,扬明,孟突丽等.日本研究多糖的新近展.国外医学中医中药分册, 1997, 19(3): 46-48
58徐梓辉,周世文,黄文权等.薏苡仁多糖对实验性糖尿病大鼠红细胞免疫、T淋巴细胞亚群的影响.湖南中医学院学报, 2001, 21(1): 17-19
59左绍远,罗华君,朱振宇.螺旋藻多糖对糖尿病小鼠抗氧化能力的影响.药物生物技术, 2001, 8(1): 36-38
60陈蔚,刘芳,俞茂华等.黄芪多糖对NOD小鼠1型糖尿病的预防作用.复旦学报(医学科学版), 2001, 28(1): 57-60
61王玲,张才军,李维波等.枸杞多糖对2型糖尿病患者T淋巴细胞亚群和细胞因子的调节作用.河北中医, 2001, 23(12): 888-890
62 L. Thorpm. Diabetic Nephropathy: Common Questions. Am Fam Physician, 2005, 72(1): 96-99
63 T. Vaimadridc, R. Kiein, E. Mosss, et al. The Risk of Cardiovascular Disease Mortality Associated with Microalbuminuria and Gross Proteinuria in Persons with Older onset Diabetes Mellitus. Arch Intern Med, 2000, 160(3): 1093-1100
64 R. Revisan, G. Viberti. Genetic Factors in the Development of Diabetic Nephropathy. J Lab Clin Med, 2002, 126(4): 342-346
65邓权.益肾活血法治疗糖尿病肾病62例.浙江中医杂志, 1996, 31(7): 317-320
66焦鹏.益气活血化瘀法治疗早期糖尿病肾病40例.新中医, 2001, 33(11): 34-36
67韩吉淼,徐文清,刘春荣.程益春教授治疗糖尿病肾病的用药经验.中国中医药信息杂志, 2001, 8(8): 72-75
68程汉桥,赵兴兰.中西医结合治疗早期糖尿病肾病23例.中国中西医结合杂志, 1996, 16(6): 364-365
69王长闵,高军,粱桂芳.中西医结合治疗糖尿病肾病肾功能不全.中医药研究, 2000, 16(4): 8-9
70张国山,陆连芬.益肾活血方治疗糖尿病肾病100例临床研究.天津中医, 2000, 17(3): 17-18
71桑岚.猪苓汤治疗糖尿病肾病35例临床报道.河南中医药学刊, 2000, 15(3): 34-35
72王亚敏.中西医结合治疗糖尿病肾病疗效观察.中国中西医结合肾病杂志, 2002, 3(4): 232-234
73周兴磊,冯志刚,张本祥.冬虫夏草治疗糖尿病肾病90例临床分析.临床医学, 2000, 20(1): 56-57
74田云龙.血塞通注射液干预治疗糖尿病肾病的临床观察.中国中西医结合杂志, 2002, 22(10): 753-755
75占永力.中药三七注射液对显性糖尿病肾病并高凝状态的影响.中国中西医结合肾病杂志, 2002, 3(1): 23-26
76王慧芳,马骏,陈国庆等.大黄对早期糖尿病肾病患者肾脏血流动力的影响.铁道医学, 2001, 29(5): 320-321
77王海松,谢春光.益肾糖泰颗粒对糖尿病大鼠肾脏病变的影响.成都中医药大学学报, 2000, 23(1): 49-51
78李怡,张前进,李秋贵等.糖肾胶囊对FFR胰岛素抵抗性与leptin浓度的影响.中国实验方剂学杂志, 2000, 6(1): 25-27
79白善信.慢性肾衰竭的中草药防治研究.中国中西医结合肾病杂志, 2001, 2(4): 246-248
80冯建春,倪青.时氏糖肾胶囊治疗糖尿病肾病的实验研究.中国实验方剂学杂志, 2000, 6(6): 32-36
81李建生.大黄蛰虫丸对老年糖尿病早期肾病TXB3和6-keto-P的影响.辽宁中医杂志, 1998, 25(10): 53-55
82徐蓉娟,李红,唐红等.治糖保肾冲剂治疗早期糖尿病肾病大鼠的实验研究.上海中医药大学学报,加00, l4(4): 47-49
83刘志红,黎磊石.糖尿病肾病发病机理.中华肾脏病杂志, 1999, 15(2): 120-123
84徐向进,吴玉水,冯修高等.槲皮素对糖尿病大鼠肾脏转化生长因子-β(TGF-β)表达的影响.中国糖尿病杂志, 2001, 9(1): 44-48
85廖璞,王淑琴,廖雪松等.银杏叶提取物对糖尿病大鼠肾脏保护作用的实验研究.中国药房, 2000, 11(3): 114-115
86李英,吴文清,张益民等.野黄芪甙原对糖尿病大鼠肾脏蛋白激酶C活性作用的研究.中华肾脏病杂志, 2000, 16(21): 89-92
87倪海祥,罗苏生,邵国民等.刺五加注射液对早期糖尿病肾脏病变及血浆、尿内皮素的影响.中国中西医结合杂志, 2001, 21(2): 105-107
88 A. Doria, J.H. Warram, A.S. Krolewski. Genetic Susceptibility to Nephropathy in Insulin Dependent Diabetes: from Epidemiology to Molecular Genetics. Diabetes/Metabolism Review, 1995, 11(1): 287-290
89 S.T. Azar, P.A. Zalloua, R. Medlej, et al. The Degenotype of the ACE Gene Polymorphism is Association with Diabetic Nephropathy in the Type-1 Diabetics. Endocr Res,2001, 27(2): 99-108
90 G. Wladylaw, K. Dariusz, M.Z. Moczulski, et a1. Role of GLUTl Gene in Susceptibility to Diabetic Nephropathy in Type 2 Diabetes. Kidney Int, 2001, 59(4): 631-636
91 A. Faneui, S. Hadjadj, Y. Gallois, et a1. Polymorphisms of Aldose Reductase Gene and Susceptibility to Retinopathy and Nephropathy in Caucasians with Type 1 Diabetes. Arch MalCoeur Vaiss, 2002, 95(1): 701-708
92 E. Noiri, H. Satoh, J. Taguchi, et a1. Association of eNOS Glu298Asp Polymorphisms with End-stage Renal Disease. Hypertension, 2002, 40(2): 535-540
93 S. Araki, D.K. Moczulski, L. Hanna, et a1. Am E Polymorphisms and the Development of Diabetic Nephropathy in Typel Diabetes: Results of Case-Control and Family-Based Studies. Diabetes, 2000, 49(3): 2190-2195
94 J.F. Moorhead, M.K. Chin, E.J. Nahasm, et al. Lipid Neophrotoxicity in Chronic Progressive Glomerulur and Tubulo-Intestinal Disease. Lancet, 1982, 2(3): 1309-1311
95 K. Zuzaki, S. kobori, M. Ide, et al. Acetyl-low Density Lipoprotein Receptor on Rat Mesangial Cells. Atherosclerosis, 2003, 101(2): 177-182
96 X.Z. Ruan, Z. Varghese, S.H. Powis, et al. Human Mesangial Cells Express Inducible Macrophage Scvenger Receptor: an Ap-1and ets Nidiated Responese. Kidney Int, 2004, 56(suppl71): S163-S166
97 R. Lehmann, E.D. Schleicher. Molecular Mechanism of Diabetic Nephropathy. Clin Chim Acta, 2000, 297(1): 135-144
98肖谦,汪恕萍.多元醇通路与糖尿病慢性并发症的关系研究进展.国外医学内分泌分册, 2001, 21(7): 128-131
99 P.A. Graven. Nitric Oxide Inhibition of Transforming Growth Factor-βand Collagen Synthesis in Mesangial Cells. Diabetes, 1997, 46(2): 871-877
100 B. Erdos, J.A. Snipes, A.W. Miller, et al. Cerebrovascular Dysfunction in Zucker Obese Rats is Mediated by Oxidative Stress and Protein Kinase C. diabetes, 2004, 53(7): 1352-1359
101 L. Brown. Biochemistry and Molecule Cell Biology of Diabetic Complication of Mellitus. Annual Rev Biochem Nature, 2001, 414(4): 813-820
102 E. Tsiani, P. Lekas, I.G. Fantus, et a1. High Glucose Enhanced Activation of Mesangial Cell p38MAPK by ET-1, ANG-2 and Platelet Derived Growth Factor. A J Physiol Endocrinol Metab, 2002, 282(1): E161-El69
103 J.A. Dlugosz, S. Munk, K. Drezgic, et a1.Stretch Induced Mesangial Cell ERKI/ERK2 Activation is Enhanced in High Glucose by Decreased. Dephosphorylation. Am J physiol Rena lPHysiol, 2000, 21(3): F688-F671
104 S.W. Kang, A.S. Gdler, L.A. Page, et al. p38MAPK and MAPK kinase3/6 mRNA and Activities are Increased in Early Diabetic Golmemli. Kidney Int, 2001, 60(2): 543-552
105 W.A. Willian, C.L. Dixon, C. Hebert, et a1. Chronic Exposure of Human Mesangial Cells to High Glucose Environments Activates the p38MAPK Pathway. Kidney lnt, 2001, 60(3): 858-871
93 S. Araki, D.K. Moczulski, L. Hanna, et a1. Am E Polymorphisms and the Development of Diabetic Nephropathy in Typel Diabetes: Results of Case-Control and Family-Based Studies. Diabetes, 2000, 49(3): 2190-2195
94 J.F. Moorhead, M.K. Chin, E.J. Nahasm, et al. Lipid Neophrotoxicity in Chronic Progressive Glomerulur and Tubulo-Intestinal Disease. Lancet, 1982, 2(3): 1309-1311
95 K. Zuzaki, S. kobori, M. Ide, et al. Acetyl-low Density Lipoprotein Receptor on Rat Mesangial Cells. Atherosclerosis, 2003, 101(2): 177-182
96 X.Z. Ruan, Z. Varghese, S.H. Powis, et al. Human Mesangial Cells Express Inducible Macrophage Scvenger Receptor: an Ap-1and ets Nidiated Responese. Kidney Int, 2004, 56(suppl71): S163-S166
97 R. Lehmann, E.D. Schleicher. Molecular Mechanism of Diabetic Nephropathy. Clin Chim Acta, 2000, 297(1): 135-144
98肖谦,汪恕萍.多元醇通路与糖尿病慢性并发症的关系研究进展.国外医学内分泌分册, 2001, 21(7): 128-131
99 P.A. Graven. Nitric Oxide Inhibition of Transforming Growth Factor-βand Collagen Synthesis in Mesangial Cells. Diabetes, 1997, 46(2): 871-877
100 B. Erdos, J.A. Snipes, A.W. Miller, et al. Cerebrovascular Dysfunction in Zucker Obese Rats is Mediated by Oxidative Stress and Protein Kinase C. diabetes, 2004, 53(7): 1352-1359
101 L. Brown. Biochemistry and Molecule Cell Biology of Diabetic Complication of Mellitus. Annual Rev Biochem Nature, 2001, 414(4): 813-820
102 E. Tsiani, P. Lekas, I.G. Fantus, et a1. High Glucose Enhanced Activation of Mesangial Cell p38MAPK by ET-1, ANG-2 and Platelet Derived Growth Factor. A J Physiol Endocrinol Metab, 2002, 282(1): E161-El69
103 J.A. Dlugosz, S. Munk, K. Drezgic, et a1.Stretch Induced Mesangial Cell ERKI/ERK2 Activation is Enhanced in High Glucose by Decreased. Dephosphorylation. Am J physiol Rena lPHysiol, 2000, 21(3): F688-F671
104 S.W. Kang, A.S. Gdler, L.A. Page, et al. p38MAPK and MAPK kinase3/6 mRNA and Activities are Increased in Early Diabetic Golmemli. Kidney Int, 2001, 60(2): 543-552
105 W.A. Willian, C.L. Dixon, C. Hebert, et a1. Chronic Exposure of Human Mesangial Cells to High Glucose Environments Activates the p38MAPK Pathway. Kidney lnt, 2001, 60(3): 858-87114(4): 481-483
119吴先旺.中西医结合治疗糖尿病肾病53例临床观察.江苏中医药, 2005, 26(2): 21-22
120曲红,王德山.枸杞多糖的药理及临床研究概况.山东医药工业, 2002, 21(4): 36-37
121罗琼,李瑾伟,张声华等.枸杞多糖-X组分对糖尿病家兔降血糖的效果.营养学报, 1997, 19(2): 173-177
122罗琼,阎俊,李瑾伟等.枸杞多糖粗品与纯品抗疲劳作用的比较.营养学报, 1999, 21(3): 310-317
123任彬彬,马永萍,沈泳等.宁夏枸杞及甜菜碱H2O2诱发PRC膜脂质过氧化的影响.中国中药杂志, 1995, 20(5): 303-304
124田丽梅,王昊.枸杞多糖的提取分离和其组成研究.中国中药杂志, 2006, 31(19): 1603-1607
125王建华.枸杞多糖的结构与保健功能评价. [武汉华中农业大学博士论文]. 2001: 17-18
126袁振林.枸杞多糖的提取及含量和分子量分布的测定.广东化工, 2003, 2(3): 43-45
127 M.M. Bradford. A rapid and Sensitive Method for the Quantification of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem, 1976, 72(2): 248-254
128张民.枸杞多糖的特性、结构及生物活性评价. [武汉华中农业大学博士论文]. 2003: 25-35
129何进,张声华.枸杞及枸杞多糖研究.食品科学, 1995, 16(2): 14-21
130黄琳娟,林颖,田庚元等.枸杞中免疫活性成分的分离纯化及物理化学性质的研究.药学学报, 1998, 33(7): 512-516
131王玲,李俊,李欣等.枸杞多糖2对辐射损伤小鼠免疫功能恢复的影响.上海免疫学杂志, 1995, 15(4): 209-212
132李晓莉,王斌,刘嘉麟等.枸杞多糖对小鼠耐缺氧效应的研究.华中农业大学学报, 1999, 18(3): 283-285
133戴春芝,文润玲,李为等.枸杞和枸杞多糖与抗衰延寿,老年学杂志, 1994, 14(1): 33-36
134 H. Sakuraba, H. Mizukami. Reduced beta-cell Mass and Expression of Oxidative Stress Related DNA Damage in the Islet of Japanese Type II Diabetic Patients. Diabetologia, 2002, 45(1): 85-96
135 J. Leinonen, T. Lehtimaki. New Biomarker Evidence of Oxidative DNA Damage in Patients with Non-Insulin-Dependent Diabetes Mellitus. FEBS Letters, 1997, 3(1): 150-152
136 Y. Hinokio, S. Suzuki. Oxidative DNA Damage in Diabetes Mellitus:its Association with Diabetic Complications. Diabetologia, 1999, 42(8): 995-998
137中华人民共和国卫生部制定发布.中药新药临床指导原则第一辑. 1993: 215-232
138郭啸华.实验性2型糖尿病大鼠模型的建立.肾脏病与透析肾移植杂志, 2000, 9(4): 351-355
139李光伟,潘孝仁, S.Lillioja等.检测人群胰岛素敏感性的一项新指标.中华内科杂志, 1993, 32(2): 656-660
140项坤三,贾伟平,陆俊茜等.中国上海地区40岁以上成人中肥胖与代谢综合症的关系.中华内科杂志, 2000, 39(2): 224-228
141朱姿英,薛耀明.高甘油三脂血症和2型糖尿病.中国糖尿病杂志, 2003, 13(2): 153-154
142 A.C. Maritim, R.A. Sanders, J.B. Watkins. Diabetes, Oxidative Stress, and Antioxidants: a review J. Biochem. Mol. Toxicol, 2003, 17(1): 24-38
143游捷.糖尿病患者外周血淋巴细胞DNA单链断裂的研究.中华内分泌代谢杂志, 1997, 13(1): 55-57
144 H.O. Adami, W.H. Chow, O. Nyren, et al. Excess Risk of Primary Liver Cancer in Patients with Diabetes Mellitus. J-Nati-Cancer-Inst, 1996, 88(20): 1472-1477
145 T. William. Insulin Resistance: Cellular and Clinical Concepts. Experimental Biology and Medicine, 2001, 226(7): 13-26
146 H.K. Karlsson, J.R. Zierath. Insulin Stimulated Phosphorylation of the AKT Substrate AS160 is Impaired in Skeletal Muscle of Type 2 Diabetic Subjects. Diabetes, 2005, 54(3): 1692-1697
147 L.R. Derek, Z. Yehiel. Recent Advances in Our Understanding of Insulin Action and Insulin Resistance. Diabetes Care, 2001, 24(3): 588-597
148 C. Alvaro, T. Teruel, R. Hernandez. et al. Tumor Necrosis Factor-alpha Produces Insulin Resistance in Skeletal Muscle by Activation of Inhibitor KappaB Kinase in a p38MAPK Dependent Manner. Journal of Biological Chemistry, 2004, 279(3): 17070-17078
149 C. Huang, R. Somwar, N. Patel, et al. Sustained Exposure of L6 Myotubes to High Glucose and Insulin Decreases Insulin Stimulated GLUT4 Translocation but Upregulates GLUT4 Activity. Diabetes, 2002, 51(7): 2090-2097
150 A. Klip, T. Ramlal, A.J. Young, et al. Insulin Induced Translocation of Glucose Transporters in Rat Hindlimb Muscles. FEBS Lett, 1987, 244(10): 224-230
151 A. Marette, C. Atgie, Z. Liu, et al. Differential Regulation of GLUT1 and GLUT4 Glucose Transporters in Skeletal Muscle of a New Model of Type 2 Diabetes. Diabetes, 1993, 42(5): l195-120l
152 L. Maianu, S.R. Keller, W.T. Garvey, et al. Adipocytes Exhibit Abnormal Subcellular Distributionand Translocation of Vescles Containing GLUT4 and Insulin Regulated Amino Peptidase in Type
2 Diabetes Mellitus: Implications Regarding Defects in Vesicle Trafficking. Clin Endocrinol Metab, 2001, 86(6): 5450-5456
153 L.W. Ileen, C. Han, J. Morris, et al. Role of Aktlprotein Kinase B in Metabolism. Trends in Endocrinology and Metabolism, 2002, 13(3): 444-451
154 H .Cho, J. Mu, J.K. Kim, et al. Insulin Resistance and a Diabetes Mellitus-like Syndrome in Mice Lacking the Protein Kinase Akt2/PKB-beta. Science, 2001, 292(1): 1728-1731
155 E.W. Christian, M.D. Lorna, K.L. Melissa, et al. Protein Kinase BlAkt Prevents Fatty Acid-Induced Apoptosis in Pancreatic Cells (INS-1). J Biol Chem, 2002, 277(3): 49676-49684
156 K.V. Kandror. A Long Search for Glut4 Activation. Sci STKE, 2003, 169(9): 5-9
157 K.F. Howlett, K. Sakamoto, M.F. Hirshman, et al. Insulin Signaling after Exercise in Insulin Receptor Substrate-2-Deficient Mice.Diabetes, 2002, 51(2): 479-483
158 J.L. Evans, I.D. Goldfine, B.A. Maddux, et al. Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes. Endocr. Rev, 2002, 23(5): 599-622
159 R. Somwar, S. Koterski, G. Sweeney, et al. A Dominant-Negative p38 MAPK Mutant and Novel Selective Inhibitors of p38MAPK Reduce Insulin-stimulated Glucose Uptake in 3T3-L1 Adipocytes without Affecting GLUT4 Translocation.J Biol Chem, 2002, 277(52): 50386-50395
160 W. Niu, C. Huang, Z. Nawaz, et al. Maturation of the Regulation of GLUT4 Activity by p38 MAPK during L6 Cell Myogenesis. Biol Chem, 2003, 278(20): 17953-17962
161 X. Xi, J. Han, J.Z. Zhang, et al. Stimulation of Glucose Transport by AMP-activated Protein Kinase via Activation of p38 Mitogen-activated Protein Kinase. J Biol Chem, 2001, 276(44): 41029-41034
162 Y. Guan, M.D. Breyer. Peroxisome Proliferator-activated Receptors (PPARs): Novel Therapeutic Targets in Renal Disease. Kidney Int, 2001, 60(1): 14-30
163 M. Brownlee. Biochemistry and Molecular Cell Biology of Diabetic Complications. Nature, 2001, 414(6865): 813-816
164 R.E. Routh, J.H. Johnson, K.J. Mccarthy, et al. Troglitazone Suppresses the Secretion of Type 1 Collagen by Mesangial Cells in Vitro. Kidney Int, 2002, 61(4): 1365-1376
165 J. Floege, C. Alpers, M.W. Burns, et al. Glomerular Cells, Extracellular Matrix Accumulation, and the Development of Glomerulosclerosis in the Remnant kidney. Lab Invest, 1992, 66(5):485-492
166李才主编.疾病模型与实验病理学.吉林大学出版社, 2002: 117-131
167 H.A. Hunjoo, L.E. Hibahl. Reactive Oxygen Species as Glucose Signaling Molecules in Mesangial Cells Cultured under Gigh Glucose. Kindry lnt, 2005, 58(suppl 77): 19-22
168 H. Ha, H.B. Lee. Reactive Oxygen Species as Glucose Signaling Molecules in Mesangial Cells Cultured under High Glucose. Kidney lnt, 2006, 7(Supp1): 19-25
169 F. Zheng, A. Fornoni, S.J. Elhot, et a1. Upregulation of TypeI Collagen by TGF-beta in Mangial Cells is Blocked by PPAR gamma Activation. Am J Physiol Renal Physiol, 2002, 282(4): F639-F643
170 T. Teruel, R. Hernandez, M. Benito, et a1. Rosiglitazone and Retinoic acid Induce Uncoupling Protein-1(UCP-1)in a p38 Mitogen Activated Protein Kinase Dependent Manner in Fetal Primary Brown Adipocytes. J Biol Chem, 2003, 278(1): 263-269
171 N. Sakai, T. Wada, K. Furuichi, et al. Involvement of Extracellular Signal Regulated Kinase and p38 in Human Diabetic Nephropathy. Am J Kidney Dis, 2005, 45(1): 54-65
172 P.C. Chang, T.H. Chen, C.J. Chang, et al. Advanced Glycosylation end Products Induce Inducible Nitric Oxide Synthase (iNOS) Expression via a p38MAPK Dependent Pathway. Kidney Int, 2004, 65(5): 1664-1675
173 H. Fujita, S. Omori, K. Ishikura, et al. ERK and p38 Mediate High Glucose Induced Hypertrophy and TGF-beta Expression in Renal Tubular Cells. Am J Physiol Renal Physiol, 2004, 286(1): F120-F126
174 S.W. Kang, S.C. Adler, J. LaPage, et al. p38 MAPK and MPAK Kinase 3/6 mRNA and Activities are Increased in Early Diabetic Golmeruli. Kidney Int, 2001, 60(2): 543-552
175 S. Kang, R. Natarajan, A. Shahed, et al. Role of 12-lipoxygenase in the Stimulation of p38 Mitogen Activated Protein Kinase and Collagen alpha5 in Experimental Diabetic Nephropathy and in Glucose Stimulated Podocytes. J Am SocN ephrol, 2003, 14(12): 3178-3187
176 C.W. Park, J.H. Kim, J.H. Lee, et al. High Glucose Induced Intercellular Adhesion Molecule-1 (ICAM) Expression through an Osmotic Effect in Rat Mesangial Cells is PKC-NF KB-dependent. Diabetes, 2000, 43(7): 1544-1557
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