参芪复方降血糖机理研究
摘要
目的：通过大鼠糖尿病模型的建立，研究参芪复方对血糖调节激素的影响及改善代谢紊乱的作用及机制。方法：采用Alloxan腹腔注射诱导糖尿病大鼠模型，并随机分为参芪复方大、中、小剂量组，西药组，模型组及正常对照组。治疗三周后，通过放射免疫、血清酶学检查等方法，测定各组大鼠空腹及餐后2小时BG，INS、GLU、GLP-1、C-P，SOD并做胰腺组织病理切片观察。结果：糖尿病大鼠存在着上述指标的明显异常。参芪复方可改善糖尿病大鼠高血糖代谢紊乱状态，提高血清胰岛素含量，降低拮抗激素水平，促进胰岛β细胞的增殖和修复，综合疗效优于西药对照组。结论：参芪复方可在多个环节、多个水平，发挥降血糖作用。
Objective:To investigate the action and mechanism of Shenqi Polypharmaceutical on how to influence diabetic rat's blood glucose regulating hormones and improve its supersession disorder state. Methods-.Established DM rats by intraperitoneal injection of Alloxan are to be diveid randomly in five groups:model control,DM model treated with low dowsage middle dowsage and high dosage of SQ and , BS group respectively.Normal control group is also set.After three week's treatment, detecting rat's following materials including BG, INS GLIK GLP-K C-P, SOD both in am empty stomach state and postprandial state with the use of radioimmuno assay and serum enzyme examination ,meanwhile rat's pancreatic tissues are also made into pathological section for analysis. ResuItrDM rats do exist abnormality of the above mentioned materials.SQ can improve the DM rat's high blood glucose metabolism disorder ,raising INS content in serum whereas taking down the GLU level ;accelerating the renovation and proliferation of the pancreatic B cells.The general curative effect of SQ is better than the west medicine corss-refer group. Conclusion:SQ can act in multiple ways and levels to degrade blood glucose.
Objective:To investigate the action and mechanism of Shenqi Polypharmaceutical on how to influence diabetic rat's blood glucose regulating hormones and improve its supersession disorder state. Methods-.Established DM rats by intraperitoneal injection of Alloxan are to be diveid randomly in five groups:model control,DM model treated with low dowsage middle dowsage and high dosage of SQ and , BS group respectively.Normal control group is also set.After three week's treatment, detecting rat's following materials including BG, INS GLIK GLP-K C-P, SOD both in am empty stomach state and postprandial state with the use of radioimmuno assay and serum enzyme examination ,meanwhile rat's pancreatic tissues are also made into pathological section for analysis. ResuItrDM rats do exist abnormality of the above mentioned materials.SQ can improve the DM rat's high blood glucose metabolism disorder ,raising INS content in serum whereas taking down the GLU level ;accelerating the renovation and proliferation of the pancreatic B cells.The general curative effect of SQ is better than the west medicine corss-refer group. Conclusion:SQ can act in multiple ways and levels to degrade blood glucose.
引文
1．2型糖尿病实用目标和治疗，亚太地区2型糖尿病政策组文1999。
2．《现代糖尿病学》，朱禧星主编，上海医科大学出版社，2000年5月第1版。
3．封银曼，张小平。消渴灵胶囊治疗2型糖尿病气阴两虚夹瘀证的临床研究，河南中医，1998，18(6)：354
4．谢春光，张发荣。糖复康治疗2型糖尿病的临床疗效观察，中医研究，1997，17(11)：23
5．周云庆。益气养阴化瘀法治疗气阴两虚型糖尿病的临床研究，江苏中医，1998，19(3)：11
6．林兰，张鸿恩。降糖通脉胶囊治疗糖尿病血管合并症的临床研究，中医杂志，1992，33(8)：26
7. Orskov C,Jepperson J,Madshad S,et al.Proglucagon products in the fasting state and after oral and intravenous arginine. J Clin lnvest, 1991,87:415
8．程益春。消渴片治疗糖尿病333例临床总结，山东中医学院学报，1985，(3)：7
9．熊曼琪。脾虚是消渴病的重要病机，广州中医学院学报，1991，(1)：1
10．王静芳96例老年糖尿病中医证候分析。上海中医药杂志，1999，(7)：21
11．张延群。2080例糖尿病患者证候与血糖关系分析，中医杂志，1996，(10)：617
12．王伟明，王翠萍，郭宝荣。浅谈糖尿病从瘀论治，山东中医杂志，1994，13(2)：52
13．赵荣华，易元琼，李永强，张秋云，唐文旭。518个糖尿病处方统计分析，云南中医学院学报，1997，20(2)：21
14．沈映君，李仪奎，陈奇等。中药药理学，第1版，上海科学技术出版社1997：161
15．王莉，李松林，王涛。降血糖植物多糖和糖甙研究进展，中药材，2000，23(9)：575-579
16．戴春笋，刘志红，陈惠萍等。大黄酸治疗STZ诱导糖尿病大鼠的远期实验研究，肾脏病与透析肾移植杂志，1999，8(5)：413
17．孙子林，葛祖恺。糖尿病动物模型及其进展，中国糖尿病杂志，1999，7(4)：227-228
18．胡建。内分泌及代谢性疾病动物模型，魏宏主编：医学实验动物学，第1版，四川科学技术出版社1998：348
19. Fehmann HC,Goke R,Goke B,Glucagon-like peptide(7-36)/(7-37)amide is a new increfin. Mol Cell Endocrinonl, 1992,85:39.
20. Montrose Rafizadeh C,Egan Jm,Roth J.lncretin hormones regulateglucose-de pendent insulin secretion in RIN 1046-38 cells. Mechanisms of action. End ocrinol, 1994,135:589.
21. Will ms B,Wemer J,Holst JJ,et al. Gastric emptying,glucose responses,and i marlin secretion after a liquid test meal:effects of exogenous glucagon-like peptide-l(GLP-1)-(7-36)amide in type 2(noninsulin-dependent)diabetic patien ts.J clin Endoerinol Metab,1996,81:327-332.
22．何泽，南红梅，南征。中医药治疗实验性糖尿病及其慢性并发症研究进展，中国中西医结合杂志，2000，20(8)：634-636
23．中药降血糖机制研究进展。新疆中医药，1998，16(2)：53
24．韩莹，屠树滋，王秋娟。治疗糖尿病药物的研究进展，中国新药杂志2000，9(7)：445
25．何进，刘皋林。餐后高血糖的药物治疗进展，解放军药学学报，17(4)：205-206
26．小野顺子，α-葡萄糖苷酶抑制剂，庄祥云译。日本医学介绍，1999，20(1)：22
27. The Diabetes Control and Complications Trial Research Group. The effect o
f intensive treatment of diabete on the development and progression of lon g-term complications on insulin-dependentdiabetes mellitus.N Engl J Med, 1 993,329:977-986
28. UK Prospective Diabetes Smdy(UKPDS)Group.Intensive bloodglucose contr ol with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. The Lancet,1998,352:837-865
29．刘秉文，陈俊杰。医学分子生物学，中国协和医科大学出版社，2000年第1版。
30. Rskov C,Poulsen SS. Glucagon-like peptide(7-36) amide receptors only in islets of Langerhans.Diabetes, 1991,40:1292
31. Valdeolmillos M,Nadal A,Contreras D,et al. The relationship between glucos e-induced k~ATP channel and the rise in [Ca~(2+) in single mouse pan creatic beta-cells. J Physiol Lond, 1992,455:173
32. Leech CA, Holz GG, mHabeber JF. Singal transduction of PACAP and GLP-1 in pancreatic beta ceils. Ann Y Acad Sci, 1996, 80:81
33. Leech CA, Holz GG, mHabeber JF. Activation of a cAMP-regulation Ca~(2+)- singaling pathway in pancreatic beta-cell by the insulinotropic h ormone glucagon-like peptide-1.Jbiol Chem, 1995,270:17749
34．苏本利，李昌城等。糖尿病患者血浆胰升糖素样肽-1(7-36)测定及其临床意义，中国糖尿病杂志，1996，4(2)：114-115
35. Gutniak M,Orskov, Holst JJ,et al. Antidiabetogenic effct of glucagon-like pep tide(7-36)amide in normal subject and patients with diabetes mellitus.N En gl J Med, 1992,130:150
36. Thorens B,Porret A,Buhler L,et al.Cloning and funcational expression of the human islet GLP-1 receptor. Diabetes,1993,42:1678
37．江清林，姜吉文，吕学诜。黄芪甲甙对类胰升血糖素肽-1作用的研究，中国
老年学杂志2003，23(1)52-53
38．江清林，姜吉文，吕学诜等。黄芪甲甙对胰岛素C肽分泌-1作用研究，黑龙江医药科学，1999，22(3)：14
39. Heikkila R E,Barden H and Choen GPrevention of alloxan-induced diabete s by ethanol administration. J Pharmacal. Exp.Ther, 190:501-506
40. Schanne F.A.X,Kane A.B,Young E.E and Father J.L.Calcium dependence of toxic cell death:A final common pathway. Sceinece,,206,700-702
41. Nayler W.G, Ferrari R and Williams A.Protective effects of pretreatment with Verapamil,Nifedipine and Propranolol on mitochodrial function in the isc heroic and reperfused myocardium.Am J Cardiol,46:242-248
42. Papaccio C,Latroico M,Frascatore S,et al. Superoxide dimutase in low-dose-s treptozotin treatedmice,a dynamic time course study. J Iht JS pancreatol, 1991,10:253
43. Matsuoka T, Kajimoto Y, Watada H,er al.Glycation dependent,reactiveoxygen species-mediated suppression of the insulin gene promoter activity in HI T cells.J Clin Invest, 1997,99:144-150
44. Faure P, et al. Clin Chem, 1993,39(5):789-793
45. Williams NR, et al.Analyst, 1995,120:887-890
46. Yang J and Cherian MG.Life Sci, 1994,1209:260-264
47. Maxwell SR, Thomason H,Sandler D,et al. Poor glycaemic control is associa tedwith reduced serum radical scavenging(antioxi-dant)activity in non-insuli n-dependent diabetes mellitus.Ann Clin Biochem ,1997,34(6):638
48. Liu K,Paterson A J,Chin E,et al. Glucose stimulates protein modification by O-linked GIcNAc in pancreatic β cells:linkage of O-linked GlcNAc to 15 cells death. Proc Natl Acad Sci USA,2000,97:2820-2825
49. Buteau J,Roduit R, Susini S,et al. Glucagon-like peptide-1 promotes DNA sy nthesis,activates phosphatidylinositol d-kinase and increases transcription fac tot pancreatic and duodenal homeobox genel(PDX-1)DNA binding activity
in beta (INS-1)-cells.Diabetologia, 1999,42:856-864
50. Xu G,Stoffers DA, Habener JF, et al.Exendin-4 stimulates both beta-cell repli cation and neogenesis,resulting in increased beta-cellmass and improved glucose tolerance in diabetic rats.Diabets,1999,48:2270-2276
51．叶山东，李素梅主编。糖尿病诊断治疗学，2000年5月第1版，安徽科学技术出版社
52．曾明德，萧树东主编。肝脏与内分泌，1995年4月第1版，人民卫生出版社。
53. Unger RH.Role of glucagons in the pathogensis of diabetes:The status of the controversy. Metabolism, 1978,27:1691
54．林伟翰。高血糖素的基础和临床，福建医大学报，1982，2：71
55. Philippe J.Structure and pancreatic expression of the insulin and glucagons genes. Endocr Rev, 1991,12:252-271
56. Freyse EJ,Becher T, EI Hag o,er al. Blood glucose lowering and glucagonost atic effect of glucagons-like peptide-1 in insulin-deprived diabetic dogs. Dia betes, 1997,46:824-828
2．《现代糖尿病学》，朱禧星主编，上海医科大学出版社，2000年5月第1版。
3．封银曼，张小平。消渴灵胶囊治疗2型糖尿病气阴两虚夹瘀证的临床研究，河南中医，1998，18(6)：354
4．谢春光，张发荣。糖复康治疗2型糖尿病的临床疗效观察，中医研究，1997，17(11)：23
5．周云庆。益气养阴化瘀法治疗气阴两虚型糖尿病的临床研究，江苏中医，1998，19(3)：11
6．林兰，张鸿恩。降糖通脉胶囊治疗糖尿病血管合并症的临床研究，中医杂志，1992，33(8)：26
7. Orskov C,Jepperson J,Madshad S,et al.Proglucagon products in the fasting state and after oral and intravenous arginine. J Clin lnvest, 1991,87:415
8．程益春。消渴片治疗糖尿病333例临床总结，山东中医学院学报，1985，(3)：7
9．熊曼琪。脾虚是消渴病的重要病机，广州中医学院学报，1991，(1)：1
10．王静芳96例老年糖尿病中医证候分析。上海中医药杂志，1999，(7)：21
11．张延群。2080例糖尿病患者证候与血糖关系分析，中医杂志，1996，(10)：617
12．王伟明，王翠萍，郭宝荣。浅谈糖尿病从瘀论治，山东中医杂志，1994，13(2)：52
13．赵荣华，易元琼，李永强，张秋云，唐文旭。518个糖尿病处方统计分析，云南中医学院学报，1997，20(2)：21
14．沈映君，李仪奎，陈奇等。中药药理学，第1版，上海科学技术出版社1997：161
15．王莉，李松林，王涛。降血糖植物多糖和糖甙研究进展，中药材，2000，23(9)：575-579
16．戴春笋，刘志红，陈惠萍等。大黄酸治疗STZ诱导糖尿病大鼠的远期实验研究，肾脏病与透析肾移植杂志，1999，8(5)：413
17．孙子林，葛祖恺。糖尿病动物模型及其进展，中国糖尿病杂志，1999，7(4)：227-228
18．胡建。内分泌及代谢性疾病动物模型，魏宏主编：医学实验动物学，第1版，四川科学技术出版社1998：348
19. Fehmann HC,Goke R,Goke B,Glucagon-like peptide(7-36)/(7-37)amide is a new increfin. Mol Cell Endocrinonl, 1992,85:39.
20. Montrose Rafizadeh C,Egan Jm,Roth J.lncretin hormones regulateglucose-de pendent insulin secretion in RIN 1046-38 cells. Mechanisms of action. End ocrinol, 1994,135:589.
21. Will ms B,Wemer J,Holst JJ,et al. Gastric emptying,glucose responses,and i marlin secretion after a liquid test meal:effects of exogenous glucagon-like peptide-l(GLP-1)-(7-36)amide in type 2(noninsulin-dependent)diabetic patien ts.J clin Endoerinol Metab,1996,81:327-332.
22．何泽，南红梅，南征。中医药治疗实验性糖尿病及其慢性并发症研究进展，中国中西医结合杂志，2000，20(8)：634-636
23．中药降血糖机制研究进展。新疆中医药，1998，16(2)：53
24．韩莹，屠树滋，王秋娟。治疗糖尿病药物的研究进展，中国新药杂志2000，9(7)：445
25．何进，刘皋林。餐后高血糖的药物治疗进展，解放军药学学报，17(4)：205-206
26．小野顺子，α-葡萄糖苷酶抑制剂，庄祥云译。日本医学介绍，1999，20(1)：22
27. The Diabetes Control and Complications Trial Research Group. The effect o
f intensive treatment of diabete on the development and progression of lon g-term complications on insulin-dependentdiabetes mellitus.N Engl J Med, 1 993,329:977-986
28. UK Prospective Diabetes Smdy(UKPDS)Group.Intensive bloodglucose contr ol with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. The Lancet,1998,352:837-865
29．刘秉文，陈俊杰。医学分子生物学，中国协和医科大学出版社，2000年第1版。
30. Rskov C,Poulsen SS. Glucagon-like peptide(7-36) amide receptors only in islets of Langerhans.Diabetes, 1991,40:1292
31. Valdeolmillos M,Nadal A,Contreras D,et al. The relationship between glucos e-induced k~ATP channel and the rise in [Ca~(2+) in single mouse pan creatic beta-cells. J Physiol Lond, 1992,455:173
32. Leech CA, Holz GG, mHabeber JF. Singal transduction of PACAP and GLP-1 in pancreatic beta ceils. Ann Y Acad Sci, 1996, 80:81
33. Leech CA, Holz GG, mHabeber JF. Activation of a cAMP-regulation Ca~(2+)- singaling pathway in pancreatic beta-cell by the insulinotropic h ormone glucagon-like peptide-1.Jbiol Chem, 1995,270:17749
34．苏本利，李昌城等。糖尿病患者血浆胰升糖素样肽-1(7-36)测定及其临床意义，中国糖尿病杂志，1996，4(2)：114-115
35. Gutniak M,Orskov, Holst JJ,et al. Antidiabetogenic effct of glucagon-like pep tide(7-36)amide in normal subject and patients with diabetes mellitus.N En gl J Med, 1992,130:150
36. Thorens B,Porret A,Buhler L,et al.Cloning and funcational expression of the human islet GLP-1 receptor. Diabetes,1993,42:1678
37．江清林，姜吉文，吕学诜。黄芪甲甙对类胰升血糖素肽-1作用的研究，中国
老年学杂志2003，23(1)52-53
38．江清林，姜吉文，吕学诜等。黄芪甲甙对胰岛素C肽分泌-1作用研究，黑龙江医药科学，1999，22(3)：14
39. Heikkila R E,Barden H and Choen GPrevention of alloxan-induced diabete s by ethanol administration. J Pharmacal. Exp.Ther, 190:501-506
40. Schanne F.A.X,Kane A.B,Young E.E and Father J.L.Calcium dependence of toxic cell death:A final common pathway. Sceinece,,206,700-702
41. Nayler W.G, Ferrari R and Williams A.Protective effects of pretreatment with Verapamil,Nifedipine and Propranolol on mitochodrial function in the isc heroic and reperfused myocardium.Am J Cardiol,46:242-248
42. Papaccio C,Latroico M,Frascatore S,et al. Superoxide dimutase in low-dose-s treptozotin treatedmice,a dynamic time course study. J Iht JS pancreatol, 1991,10:253
43. Matsuoka T, Kajimoto Y, Watada H,er al.Glycation dependent,reactiveoxygen species-mediated suppression of the insulin gene promoter activity in HI T cells.J Clin Invest, 1997,99:144-150
44. Faure P, et al. Clin Chem, 1993,39(5):789-793
45. Williams NR, et al.Analyst, 1995,120:887-890
46. Yang J and Cherian MG.Life Sci, 1994,1209:260-264
47. Maxwell SR, Thomason H,Sandler D,et al. Poor glycaemic control is associa tedwith reduced serum radical scavenging(antioxi-dant)activity in non-insuli n-dependent diabetes mellitus.Ann Clin Biochem ,1997,34(6):638
48. Liu K,Paterson A J,Chin E,et al. Glucose stimulates protein modification by O-linked GIcNAc in pancreatic β cells:linkage of O-linked GlcNAc to 15 cells death. Proc Natl Acad Sci USA,2000,97:2820-2825
49. Buteau J,Roduit R, Susini S,et al. Glucagon-like peptide-1 promotes DNA sy nthesis,activates phosphatidylinositol d-kinase and increases transcription fac tot pancreatic and duodenal homeobox genel(PDX-1)DNA binding activity
in beta (INS-1)-cells.Diabetologia, 1999,42:856-864
50. Xu G,Stoffers DA, Habener JF, et al.Exendin-4 stimulates both beta-cell repli cation and neogenesis,resulting in increased beta-cellmass and improved glucose tolerance in diabetic rats.Diabets,1999,48:2270-2276
51．叶山东，李素梅主编。糖尿病诊断治疗学，2000年5月第1版，安徽科学技术出版社
52．曾明德，萧树东主编。肝脏与内分泌，1995年4月第1版，人民卫生出版社。
53. Unger RH.Role of glucagons in the pathogensis of diabetes:The status of the controversy. Metabolism, 1978,27:1691
54．林伟翰。高血糖素的基础和临床，福建医大学报，1982，2：71
55. Philippe J.Structure and pancreatic expression of the insulin and glucagons genes. Endocr Rev, 1991,12:252-271
56. Freyse EJ,Becher T, EI Hag o,er al. Blood glucose lowering and glucagonost atic effect of glucagons-like peptide-1 in insulin-deprived diabetic dogs. Dia betes, 1997,46:824-828