金糖宁及消渴丸降糖机制的实验及临床研究
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摘要
目的
实验研究金糖宁和消渴丸中药成分对大鼠肠黏膜α-葡萄糖苷酶是否有抑制作用,并采用随机对照试验观察金糖宁对糖尿病患者的治疗作用及副作用,以探讨中成药的降糖作用机制。
方法
用大鼠小肠上段提取α-葡萄糖苷酶,按1：5倍稀释使酶反应速度达到试剂盒测定要求。以10g·L-1蔗糖作为底物,1g·L-1阿卡波糖为阳性对照,分别加入不同浓度的金糖宁、消渴丸全药、消渴丸中药、格列本脲,37℃反应40min后,在550nm波长下测定吸光度(A)。通过测定反应体系中葡萄糖生成量并计算酶活性的抑制率来判断金糖宁及消渴丸中药成分对大鼠肠黏膜α-葡萄糖苷酶活性的影响。
300例病程1年以内未规律服用口服降糖药或注射胰岛素的2型糖尿病患者或糖尿病前期患者,随机分为对照组100人；实验组200人。其中对照组餐前嚼服阿卡波糖50mg,每天3次。实验组餐前口服金糖宁胶囊4粒,每天3次。观察两组患者治疗8周后空腹及餐后2小时血糖、糖化血红蛋白(HbAlc)、血压(BP)、脉搏(P)、身高、体重、肝功能、肾功能、尿白蛋白肌酐比(ACR)、血尿常规、空腹胰岛素、血脂、血液粘度、高敏C反应蛋白(CRP),谷氨酰转移酶(GGT)的变化。
结果
阿卡波糖(1g·L-1)对α-葡萄糖苷酶的抑制率为86.3%。金糖宁(2～200mg·L-1)对α-葡萄糖苷酶的抑制率为75.6%-98.5%。消渴丸中药成分(2～200mg·L-1)对a-葡萄糖苷酶有一定的抑制作用(抑制率18.8%-35.7%)。临床随机对照试验中,金糖宁和对照组阿卡波糖相比,在空腹血糖,空腹胰岛素,早餐后血糖,糖化血红蛋白,尿酮体,胆固醇,HDL-C, LDL-C,体重,血液粘度,肝功能方面的作用未见统计学差异(P>0.05)。对入组患者甘油三酯的降低作用有统计学意义(P<0.05)。
结论
金糖宁对大鼠小肠黏膜α-葡萄糖苷酶有显著的抑制作用,消渴丸中药成分对大鼠小肠黏膜α-葡萄糖苷酶具有一定抑制作用。临床随机对照试验中,金糖宁对降低入组患者空腹血糖、早餐后2小时血糖及糖化血红蛋白有显著作用,对血脂代谢也有改善作用。
Objective
To study whether Jintangning and Xiaoke pill's herbal composition have the inhibiting effect on the a-glucosidase through experiments and a randomized controlled trial. To find out the hypoglycemic mechanism of Jintangning and Xiaoke pill.
Methods
The a-glucosidase was prepared from the upper part of rat small intestine and diluted by5times in order to reach the requirement of the kit. Sucrose (10g·L-1) was used as the substrate, and acarbose (1g· L-1) as the positive control. Different concentrations of Jintangning, Xiaoke pill, herbal composition and glibenclamide were added into the reaction system. Measure the absorbance of the system at550nm after reacting for40min under the temperature of37℃. The a-glucosidase activity was detected by measuring the concentration of glucose produced. The inhibition ratio was calculated in order to determine whether Jintangning and the herbal composition of Xiaoke pill have the inhibiting effect on the a-glucosidase.
A total of300participants with a primary diagnosis of type2diabetes or impaired glucose tolerance were included and randomized into two groups,200in the experiment group and100in the control. The participants in the experiment group took Jingtangning4pills before meals, three times a day, while the control group chewed Acarbose50mg before meals three times a day. Measure their blood glucose fasting and after breakfast, HbAlc, blood pressure (BP), pulse (P), height, weight, liver function, renal function, Albumin-to-Creatinine Ratio (ACR), blood and urine routine test, fasting insulin, blood lipid, blood viscosity, C-reactive protein (CRP) and gamma-glutamyl transpeptidase (GGT) after8-week-treatment.
Results
Acarbose (1g·L-1) was shown to be an a-glucosidase inhibitor with an evident inhibition ratio (86.3%). Jintangning (2～200mg·L-1) has an inhibition ratio of75.6%-98.5%. The herbal composition of Xiaoke pill (2～200mg·L-1) has an inhibition ratio of18.8%-35.7%. In the Randomized Controlled Trial, it was no statistical difference between Acarbose and Jingtangning on fasting blood-glucose, fasting insulin, blood-glucose after breakfast, HbAlc, urine ketone bodies, cholesterol, HDL-C, LDL-C, body weight, blood viscosity and liver function (P>0.05). There was statistical difference (P<0.05) between Acarbose and Jingtangning on the effect of triglyceride reducing.
Conclusions
Jintangning has obivious inhibiting effects on the a-glucosidase of rat small intestine. The herbal composition of Xiaoke pill has some inhibiting effects on the a-glucosidase of rat small intestine. In the Randomized Controlled Trial, Jintangning has reducing effects on fasting blood-glucose, blood-glucose after breakfast and HbAlc. It can also ameliorate the disorder of lipid metabolism.
实验研究金糖宁和消渴丸中药成分对大鼠肠黏膜α-葡萄糖苷酶是否有抑制作用,并采用随机对照试验观察金糖宁对糖尿病患者的治疗作用及副作用,以探讨中成药的降糖作用机制。
方法
用大鼠小肠上段提取α-葡萄糖苷酶,按1：5倍稀释使酶反应速度达到试剂盒测定要求。以10g·L-1蔗糖作为底物,1g·L-1阿卡波糖为阳性对照,分别加入不同浓度的金糖宁、消渴丸全药、消渴丸中药、格列本脲,37℃反应40min后,在550nm波长下测定吸光度(A)。通过测定反应体系中葡萄糖生成量并计算酶活性的抑制率来判断金糖宁及消渴丸中药成分对大鼠肠黏膜α-葡萄糖苷酶活性的影响。
300例病程1年以内未规律服用口服降糖药或注射胰岛素的2型糖尿病患者或糖尿病前期患者,随机分为对照组100人；实验组200人。其中对照组餐前嚼服阿卡波糖50mg,每天3次。实验组餐前口服金糖宁胶囊4粒,每天3次。观察两组患者治疗8周后空腹及餐后2小时血糖、糖化血红蛋白(HbAlc)、血压(BP)、脉搏(P)、身高、体重、肝功能、肾功能、尿白蛋白肌酐比(ACR)、血尿常规、空腹胰岛素、血脂、血液粘度、高敏C反应蛋白(CRP),谷氨酰转移酶(GGT)的变化。
结果
阿卡波糖(1g·L-1)对α-葡萄糖苷酶的抑制率为86.3%。金糖宁(2～200mg·L-1)对α-葡萄糖苷酶的抑制率为75.6%-98.5%。消渴丸中药成分(2～200mg·L-1)对a-葡萄糖苷酶有一定的抑制作用(抑制率18.8%-35.7%)。临床随机对照试验中,金糖宁和对照组阿卡波糖相比,在空腹血糖,空腹胰岛素,早餐后血糖,糖化血红蛋白,尿酮体,胆固醇,HDL-C, LDL-C,体重,血液粘度,肝功能方面的作用未见统计学差异(P>0.05)。对入组患者甘油三酯的降低作用有统计学意义(P<0.05)。
结论
金糖宁对大鼠小肠黏膜α-葡萄糖苷酶有显著的抑制作用,消渴丸中药成分对大鼠小肠黏膜α-葡萄糖苷酶具有一定抑制作用。临床随机对照试验中,金糖宁对降低入组患者空腹血糖、早餐后2小时血糖及糖化血红蛋白有显著作用,对血脂代谢也有改善作用。
Objective
To study whether Jintangning and Xiaoke pill's herbal composition have the inhibiting effect on the a-glucosidase through experiments and a randomized controlled trial. To find out the hypoglycemic mechanism of Jintangning and Xiaoke pill.
Methods
The a-glucosidase was prepared from the upper part of rat small intestine and diluted by5times in order to reach the requirement of the kit. Sucrose (10g·L-1) was used as the substrate, and acarbose (1g· L-1) as the positive control. Different concentrations of Jintangning, Xiaoke pill, herbal composition and glibenclamide were added into the reaction system. Measure the absorbance of the system at550nm after reacting for40min under the temperature of37℃. The a-glucosidase activity was detected by measuring the concentration of glucose produced. The inhibition ratio was calculated in order to determine whether Jintangning and the herbal composition of Xiaoke pill have the inhibiting effect on the a-glucosidase.
A total of300participants with a primary diagnosis of type2diabetes or impaired glucose tolerance were included and randomized into two groups,200in the experiment group and100in the control. The participants in the experiment group took Jingtangning4pills before meals, three times a day, while the control group chewed Acarbose50mg before meals three times a day. Measure their blood glucose fasting and after breakfast, HbAlc, blood pressure (BP), pulse (P), height, weight, liver function, renal function, Albumin-to-Creatinine Ratio (ACR), blood and urine routine test, fasting insulin, blood lipid, blood viscosity, C-reactive protein (CRP) and gamma-glutamyl transpeptidase (GGT) after8-week-treatment.
Results
Acarbose (1g·L-1) was shown to be an a-glucosidase inhibitor with an evident inhibition ratio (86.3%). Jintangning (2～200mg·L-1) has an inhibition ratio of75.6%-98.5%. The herbal composition of Xiaoke pill (2～200mg·L-1) has an inhibition ratio of18.8%-35.7%. In the Randomized Controlled Trial, it was no statistical difference between Acarbose and Jingtangning on fasting blood-glucose, fasting insulin, blood-glucose after breakfast, HbAlc, urine ketone bodies, cholesterol, HDL-C, LDL-C, body weight, blood viscosity and liver function (P>0.05). There was statistical difference (P<0.05) between Acarbose and Jingtangning on the effect of triglyceride reducing.
Conclusions
Jintangning has obivious inhibiting effects on the a-glucosidase of rat small intestine. The herbal composition of Xiaoke pill has some inhibiting effects on the a-glucosidase of rat small intestine. In the Randomized Controlled Trial, Jintangning has reducing effects on fasting blood-glucose, blood-glucose after breakfast and HbAlc. It can also ameliorate the disorder of lipid metabolism.
引文
[1]桂建华.消渴丸的安全合理使用[J].中医药信息,2009,26(1)：91.
[2]邬伟魁,张海燕,宋伟,等.糖尿病血管并发症的中药防治[J].中国实验方剂学杂志,2011,17(19)：292.
[3]张萌佳,张洁.糖尿病肾病中医药临床研究进展[J].中国实验方剂学杂志,2009,15(7)：95.
[4]胡凤平,冯所安,邓慧敏.消渴丸与优降糖治疗糖尿病的疗效对比研究[J].中药新药与临床药理,1999,5(10)：144.
[5]Goke B, Herrmann-Rinke C. The evolving role of alpha-glucosidase inhibitors[J]. Diabetes Metab Rev,1998,14:1S31.
[6]王吉耀,主编.内科学(下册)[M].北京：人民卫生出版社,2008.988.
[7]李时珍.本草纲目(虫部)[M].北京：中医古籍出版社,2008.687.
[8]张伯爽,主编.中医内科学[M].北京：人民卫生出版社,1994.586.
[9]林志强,治疗2型糖尿病的新中药制剂——金糖宁胶囊研发概况[J].海峡药学,2006,18(3)：104-105.
[10]KIM Y M, HYEON M, RHOE H I. A novel a-glucosidase inhibitor from pine bark[J]. Carbohydr Res,2004,339 (3):715.
[11]李雪宁,陈伟力,徐红蓉,等.国产格列本脲和二甲双胍复方制剂在健康志愿者的药代动力学和生物等效性[J].中国临床药理学杂志,2004,20(5)：354.
[12]张冉,刘泉,申竹芳,等.应用α-葡萄糖苷酶抑制剂高通量筛选模型筛选降血糖中药[J].中国药学杂志,2007,5：470.
[13]史轶蘩,主编.协和内分泌和代谢学[M].北京：科学出版社,1999.1334.
[14]蒲翔,冯泳,何前松,等.理气活血法对2型糖尿病模型大鼠血瘀状态的影响[J].中国实验方剂学杂志,2010,16(12)：136.
[15]吴金环,顾红岩,喇孝瑾,等.地黄与熟地黄对糖尿病小鼠血糖血脂的影响[J].中国实验方剂学杂志,2011,17(8)：161.
[16]王春怡,陈艳芬,李卫民,等.黄芪葛根汤对实验性糖尿病及胰岛素抵抗的影响[J].中国实验方剂学杂志,2011,17(16)：144.
[17]Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35):prospective observational study[J]. BMJ,2000,321:405.
[18]李家邦,高鹏翔,主编.中医学[M].北京：人民卫生出版社,2007.366.
[19]范军星,王文娟,吴凡,等.城市社区糖尿病患者治疗和控制现状研究[J].中国慢性病预 防与控制,2008,16(4)：340.
[20]倪青.中医治疗糖尿病需扬长避短[J].药品评价,2011,8(5)：42-44.
[21]林兰.现代中医糖尿病学[M].北京：人民卫生出版社,2008.223.
[22]洪绯.金糖宁胶囊的抗糖尿病作用药效研究[J].中国糖尿病杂志,2009,17(3)：181-186.
[23]林进生.金糖宁胶囊治疗2型糖尿病120例临床观察[J].世界中医药,2008,7(3)：213-214.
[24]向红丁.三五防糖法[M].北京：金盾出版社,2012.1.
[25]李秀钧,董砚虎,程丽霞,等.糖尿病研究进展——第16界国际糖尿病联盟大会纪要[J].中华内分泌代谢杂志,1998,14：72-77.
[26]向红丁.血糖测定的临床应用及再评价[J].中国实用内科杂志,2000,20(4)：206-207.
[27]Ye F, Shen ZF, Xie MZ, Alpha-glucosidase inhibition from a Chinses medical herb (Ramulus mori) in normal and diabetic rats and mice[J]. Phytomedicine,2002,9:S161-166.
[28]Van de Laar FA, Lucassen PLBJ, Akkermans RP, et al. Alpha-glucosidase inhibitors for type 2 diabetes mellitus[J]. The Cochrane Library,2009,1:1-84.
[29]迟家敏.糖尿病合并血脂代谢异常的药物治疗[J].中国新药杂志,2011,20(21)：2086-2089.
[30]Mexfarlae DP, Paterson KR, Fisher M, Oral antidiabetic agents as cardiovascular drugs[J]. Diabetes Obes Metab,2007,9:S23-30.
[31]常友成.2型糖尿病患者尿微量白蛋白肌酐比与血糖水平的相关性分析[J].中国临床研究,2010,23(12)：1116.
[2]邬伟魁,张海燕,宋伟,等.糖尿病血管并发症的中药防治[J].中国实验方剂学杂志,2011,17(19)：292.
[3]张萌佳,张洁.糖尿病肾病中医药临床研究进展[J].中国实验方剂学杂志,2009,15(7)：95.
[4]胡凤平,冯所安,邓慧敏.消渴丸与优降糖治疗糖尿病的疗效对比研究[J].中药新药与临床药理,1999,5(10)：144.
[5]Goke B, Herrmann-Rinke C. The evolving role of alpha-glucosidase inhibitors[J]. Diabetes Metab Rev,1998,14:1S31.
[6]王吉耀,主编.内科学(下册)[M].北京：人民卫生出版社,2008.988.
[7]李时珍.本草纲目(虫部)[M].北京：中医古籍出版社,2008.687.
[8]张伯爽,主编.中医内科学[M].北京：人民卫生出版社,1994.586.
[9]林志强,治疗2型糖尿病的新中药制剂——金糖宁胶囊研发概况[J].海峡药学,2006,18(3)：104-105.
[10]KIM Y M, HYEON M, RHOE H I. A novel a-glucosidase inhibitor from pine bark[J]. Carbohydr Res,2004,339 (3):715.
[11]李雪宁,陈伟力,徐红蓉,等.国产格列本脲和二甲双胍复方制剂在健康志愿者的药代动力学和生物等效性[J].中国临床药理学杂志,2004,20(5)：354.
[12]张冉,刘泉,申竹芳,等.应用α-葡萄糖苷酶抑制剂高通量筛选模型筛选降血糖中药[J].中国药学杂志,2007,5：470.
[13]史轶蘩,主编.协和内分泌和代谢学[M].北京：科学出版社,1999.1334.
[14]蒲翔,冯泳,何前松,等.理气活血法对2型糖尿病模型大鼠血瘀状态的影响[J].中国实验方剂学杂志,2010,16(12)：136.
[15]吴金环,顾红岩,喇孝瑾,等.地黄与熟地黄对糖尿病小鼠血糖血脂的影响[J].中国实验方剂学杂志,2011,17(8)：161.
[16]王春怡,陈艳芬,李卫民,等.黄芪葛根汤对实验性糖尿病及胰岛素抵抗的影响[J].中国实验方剂学杂志,2011,17(16)：144.
[17]Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35):prospective observational study[J]. BMJ,2000,321:405.
[18]李家邦,高鹏翔,主编.中医学[M].北京：人民卫生出版社,2007.366.
[19]范军星,王文娟,吴凡,等.城市社区糖尿病患者治疗和控制现状研究[J].中国慢性病预 防与控制,2008,16(4)：340.
[20]倪青.中医治疗糖尿病需扬长避短[J].药品评价,2011,8(5)：42-44.
[21]林兰.现代中医糖尿病学[M].北京：人民卫生出版社,2008.223.
[22]洪绯.金糖宁胶囊的抗糖尿病作用药效研究[J].中国糖尿病杂志,2009,17(3)：181-186.
[23]林进生.金糖宁胶囊治疗2型糖尿病120例临床观察[J].世界中医药,2008,7(3)：213-214.
[24]向红丁.三五防糖法[M].北京：金盾出版社,2012.1.
[25]李秀钧,董砚虎,程丽霞,等.糖尿病研究进展——第16界国际糖尿病联盟大会纪要[J].中华内分泌代谢杂志,1998,14：72-77.
[26]向红丁.血糖测定的临床应用及再评价[J].中国实用内科杂志,2000,20(4)：206-207.
[27]Ye F, Shen ZF, Xie MZ, Alpha-glucosidase inhibition from a Chinses medical herb (Ramulus mori) in normal and diabetic rats and mice[J]. Phytomedicine,2002,9:S161-166.
[28]Van de Laar FA, Lucassen PLBJ, Akkermans RP, et al. Alpha-glucosidase inhibitors for type 2 diabetes mellitus[J]. The Cochrane Library,2009,1:1-84.
[29]迟家敏.糖尿病合并血脂代谢异常的药物治疗[J].中国新药杂志,2011,20(21)：2086-2089.
[30]Mexfarlae DP, Paterson KR, Fisher M, Oral antidiabetic agents as cardiovascular drugs[J]. Diabetes Obes Metab,2007,9:S23-30.
[31]常友成.2型糖尿病患者尿微量白蛋白肌酐比与血糖水平的相关性分析[J].中国临床研究,2010,23(12)：1116.