胰高血糖素样肽-1类似物(JC003)对糖尿病大鼠血糖及胰岛功能的影响

Effects of GLP-1 analog(JC003) on blood glucose and pancreatic functions of diabetes mellitus in rats

目的探讨胰高血糖素样肽-1类似物(JC003)对实验性糖尿病血糖和胰岛功能的影响。方法84只Wistar大鼠,采用高脂饮食和注射40 mg/kg链脲佐菌素(STZ)方法建立实验性糖尿病动物模型。JC003治疗14 d后,采用酶化学方法检测空腹血糖;采用放射免疫方法检测血清胰岛素和C肽。胰腺组织切片HE染色和链霉菌抗生物素-过氧化物酶(SABC)免疫组化染色方法对胰岛结构和胰岛素表达情况进行观察。结果JC003中剂量组(10μg/kg)、高剂量组(100μg/kg)与糖尿病模型组比较血糖明显降低(P<0.01);中剂量组(10μg/kg)、高剂量组(100μg/kg)的血清胰岛素和C肽水平明显高于糖尿病模型组(P<0.05);JC003各剂量组对糖尿病大鼠的胰岛组织结构有显著的保护作用,并且可以增加胰岛素表达阳性的β细胞(P<0.01)。结论JC003可以通过保护大鼠胰岛细胞免受STZ的伤害和增加胰岛β细胞数量来增加胰岛素的表达和分泌,从而降低糖尿病动物血糖。

Objective To investigate the therapeutic effects of glucagon-like peptide-1 analog （JC003） on blood glucose and pancreatic functions of diabetes mellitus in rats. Methods A total of 84 Wistar rats were used in this experiment. Diabetes mellitus animal models were induced with high-fat diet and injection of 40 mg/kg streptozotociul （STZ）. After 14 d of JC003 therapy, the level of fasting plasma glucose （FPG） was detected with enzyme-chemical method. The level of serum insulin and C-peptide were measured with immunoradiometric assay method. Serial pancreatic sections were made and stained with hematoxylin-eosin （HE） and streptavidin-biotin- peroxidase complex （SABC）. Results After 14 d of JC003 injection, the level of FPG in medium-dose group （10 μg/kg） and high-dose group （100μg/kg） was lower than that in diabetes mellitus （DM） group （P〈0.01）. The level of serum insulin and C-peptide of medium-dose group （10μg/kg） and high-dose group （100μg/kg） was higher than in DM group （P 〈 0. 05）. JC003 could protect pancreatic islet from injury of STZ and increase insulin- expressing positive rate （P〈0.01）. Conclusion GLP-1 analog （JC003） can lower the level of blood glucose of diabetes mellitus through protecting pancreatic islet β cells and increasing insulin expression and secretion.