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浙江大学学报（医学版）
浙江大学学报（医学版）  2016, Vol. 45 Issue (5): 486-492    DOI: 10.3785/j.issn.1008-9292.2016.09.06
中药分子药理专题     
小檗碱抑制肠道二肽基肽酶-Ⅳ的降糖机制研究
王结胜1, 戴关海2, 李唯佳3
1. 浙江省立同德医院干部保健科, 浙江 杭州 310012;
2. 浙江省中医药研究院基础实验所, 浙江 杭州 310007;
3. 浙江省立同德医院内分泌科, 浙江 杭州 310012
Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ
WANG Jiesheng1, DAI Guanhai2, LI Weijia3
1. Department of Cadre Health, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China;
2. Basic Laboratory, Institute of Traditional Chinese Medicine of Zhejiang Province, Hangzhou 310007, China;
3. Department of Endocrinology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
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摘要：

目的：探讨短疗程口服小檗碱对糖尿病大鼠模型的作用及相关机制。方法：取健康雄性SD大鼠60只，采用腹腔注射链脲佐菌素建立糖尿病大鼠模型，其中造模成功50只，按照每天灌喂不同药物将大鼠随机分为五组：模型对照组，西格列汀组（磷酸西格列汀10 mg/kg）和小檗碱小剂量组（小檗碱30 mg/kg）、中剂量组（小檗碱60 mg/kg）、大剂量组（小檗碱120 mg/kg）。第三天早晨空腹采血，喂药后半小时予灌喂50%葡萄糖水（2 g/kg），灌喂葡萄糖2 h时采集血液和肠道标本，采用生化分析仪检测空腹血糖及餐后2 h血糖，采用ELISA法检测餐后2 h血胰岛素、胰高血糖素样肽-1（GLP-1）、二肽基肽酶-Ⅳ（DPP-Ⅳ）及局部肠道组织GLP-1、DPP-Ⅳ含量。结果：干预后小檗碱各剂量组的空腹血糖水平、餐后2 h血DPP-Ⅳ水平与模型对照组差异无统计学意义（均P>0.05）；小檗碱中、大剂量组的餐后2 h血GLP-1水平、血胰岛素水平比模型对照组升高，餐后2 h血糖水平比模型对照组降低（均P<0.05）；小檗碱各剂量组的肠道组织餐后2 h GLP-1含量比模型对照组增加，餐后2 h肠道组织DPP-Ⅳ含量比模型对照组减少（均P<0.05）。结论：短疗程口服中、大剂量小檗碱能降低糖尿病大鼠模型的餐后血糖，抑制肠道局部的DPP-Ⅳ可能是口服小檗碱的降糖机制之一，DPP-Ⅳ抑制剂的疗效可能与该药的肠道药代动力学有关。
关键词： 糖尿病/药物疗法;  小檗碱/药理学;  小檗碱/投药和剂量;  胰高血糖素样肽1/药物作用;  抗原,CD26/药物作用;  血糖/血液;  糖尿病,实验性    
Abstract:

Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg-1·d-1), low-dose berberine group (30 mg·kg-1·d-1), moderate-dose berberine group (60 mg·kg-1·d-1), and high-dose berberine group (120 mg·kg-1·d-1). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit. Results: No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all P>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all P<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all P<0.05). Conclusions: Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.
Key words: Diabetes mellitus/drug therapy    Berberine/pharmacology    Berberine/administration &    dosage    Glucagon-like peptide 1/drug effects    Antigens, CD26/drug effects    Blood glucose/blood    Diabetes mellitus, experimental
收稿日期: 2016-01-19 出版日期: 2016-09-25
CLC:  R587.1  
基金资助:

浙江省医药卫生科技计划（KYB051）；浙江省中西医结合学会科研项目（2013LYZD011）
通讯作者: 李唯佳(1963-),学士,主任中医师,主要从事胃肠道激素和糖尿病的研究;E-mail:liweijia0209@163.com;http://orcid.org/0000-0003-0681-1421     E-mail: liweijia0209@163.com
作者简介: 王结胜(1972-),硕士,副主任医师,主要从事胃肠道激素和糖尿病的研究;E-mail:wwjjss2000@163.com;http://orcid.org/0000-0002-6155-2103
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引用本文:

王结胜 等. 小檗碱抑制肠道二肽基肽酶-Ⅳ的降糖机制研究[J]. 浙江大学学报（医学版）, 2016, 45(5): 486-492.

WANG Jiesheng, DAI Guanhai, LI Weijia. Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ. Journal of ZheJiang University(Medical Science), 2016, 45(5): 486-492.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2016.09.06    或    http://www.zjujournals.com/med/CN/Y2016/V45/I5/486

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