甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用

doi:10.3969/j.issn.1006-7795.2016.05.018

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (5): 646-650.doi: 10.3969/j.issn.1006-7795.2016.05.018

甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用

宋紫辉, 张慧霞, 项宗尚, 范明源, 蔡永明, 张宗鹏

天津药物研究院新药评价有限公司, 天津 300301

收稿日期:2016-02-03 出版日期:2016-10-21 发布日期:2016-10-19
通讯作者: 张宗鹏 E-mail:zhangzp@tjipr.com
基金资助:
国家科技重大专项（2013ZX09302301）。

Antihyperglycemic effect of glargine injection in rat model of type 1 diabetes

Song Zihui, Zhang Huixia, Xiang Zongshang, Fan Mingyuan, Cai Yongming, Zhang Zongpeng

Tianjin Institute of Pharmaceutical Research New Drug Evaluation Company Limited, Tianjin 300301, China

Received:2016-02-03 Online:2016-10-21 Published:2016-10-19
Supported by:
This study was supported by National Science and Technology Major Project(2013ZX09302301).

摘要/Abstract

摘要： 目的采用链脲佐菌素（streptozotocin，STZ）诱导的大鼠1型糖尿病（insulin-dependent diabetes mellitus，IDDM）模型，评价甘精胰岛素注射液的降血糖作用。方法健康雄性SD大鼠，单次尾静脉注射2%（质量分数）STZ 58 mg/kg制备IDDM模型，采用随机数字表法将造模成功的动物（禁食血糖≥16.7 mmol/L）分为供试品甘精胰岛素注射液（glargine injection）低、中和高3个剂量组、参照药来得时（Lantus）中剂量组和模型对照组，每组15只；同时设正常对照组。各组动物分别皮下注射甘精胰岛素、来得时或等体积的溶媒，每天给药，连续给药9周。每周定时检测大鼠随机血糖、体质量、摄食量和饮水量；给药结束后，采用全自动生化分析仪检测血清中尿素氮（blood urea nitrogen，BUN）、肌酐（creatinine，Cr）、总胆固醇（total cholesterol，TC）和三酰甘油（triglyceride，TG）；采用比色法定量检测糖化血红蛋白（glycosylated hemoglobin，GHb）。结果与模型对照组相比，甘精胰岛素注射液各剂量组大鼠：①体质量增加、摄食量减少；②给药后1 h血糖开始降低，2 h降至最低，8 h基本恢复到给药前，且具有剂量依赖性；③GHb不同程度地降低，具有明显的剂量-效应关系；④血清中BUN和TG降低。结论在4~8 IU/kg剂量范围内，每日皮下注射2次甘精胰岛素注射液，明显改善IDDM模型大鼠的高血糖症状，其作用效果与来得时相当；连续给药9周后，模型大鼠的血清BUN、TG和GHb显著降低，提示其具有保护肾功能、调节血脂的作用，并能减少糖尿病合并症的发生。

关键词: 链脲佐菌素, 1型糖尿病, 甘精胰岛素, 糖化血红蛋白

Abstract: Objective To evaluate the antihyperglycemic effect of glargine in streptozotocin (STZ)-induced type 1 diabetes in rats. Methods Hyperglycemic type 1 diabetic rats were obtained by intravenous injection of 2% STZ at the dose of 58 mg/kg and the success was adjudged by fasting glucose (≥ 16.7 mmol/L) within 3 consecutive days. Subsequently, 75 hyperglycemic rats were divided into five groups randomly and were treated with different doses of glargine, Lantus or control vehicle for 9 weeks, respectively. Meanwhile, a group consisted of 15 euglycemic rats was regarded as the control group and injected with control vehicle as well. Blood glucose levels, body weights, food intake and water intake in chow fed rats were measured weekly. Serum blood urea nitrogen (BUN), creatinine (Cr), total cholesterol (TC) and triglyceride (TG) were determined by automatic analyzer and glycosylated hemoglobin (GHb) was measured by rat glycosylated hemoglobin assay kits. Results Compared with model-control, an increase in body weight and a decrease in food intake were observed in rats treated with different doses of glargine. Also, glycemic levels in glargine group rats began to decline at 1 h post-injection, achieved minimally at 2 h and maintained for the following 8 hours. The reduction of GHb was dose-dependent and the decrease of serum concentration of BUN and TG was significant. Conclusion Glargine, consistent with Lantus, can lower the blood glucose in STZ-induced type 1 diabetic rats remarkably when injected twice daily with the dose of 4~8 IU/kg. It has the potent protection of kidney and regulation of blood lipid by decreasing serum concentration of BUN and TG, and could reduce the risk of diabetes complications by decreasing GHb level, as well.

Key words: streptozotocin (STZ), type 1 diabetes, glargine, glycosylated hemoglobin(GHb)

中图分类号:

宋紫辉, 张慧霞, 项宗尚, 范明源, 蔡永明, 张宗鹏. 甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用[J]. 首都医科大学学报, 2016, 37(5): 646-650.

Song Zihui, Zhang Huixia, Xiang Zongshang, Fan Mingyuan, Cai Yongming, Zhang Zongpeng. Antihyperglycemic effect of glargine injection in rat model of type 1 diabetes[J]. Journal of Capital Medical University, 2016, 37(5): 646-650.

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甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用

Antihyperglycemic effect of glargine injection in rat model of type 1 diabetes

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