胰高血糖素样肽-1类似物对实验性糖尿病大鼠的治疗作用

目的：探讨胰高血糖素样肽-1（GLP-1）类似物对实验性糖尿病的治疗作用。方法：84只Wistar大鼠随机分为正常对照组、高脂饲料组、GLP-1类似物低剂量组、GLP-1类似物中剂量组、GLP-1类似物高剂量组、糖尿病模型组和阳性对照组。采用高脂饲料饲养和注射40 mg?kg^-1 STZ方法建立实验性糖尿病动物模型。GLP-1类似物低、中、高剂量(1、10和100 μg?kg^-1)治疗7及14 d后，采用酶化学方法检测空腹血糖（FPG）；治疗14 d后，采用酶化学方法检测血清总胆固醇(TC)、血清甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)；采用放射免疫方法检测血清胰岛素和C肽。结果：GLP-1类似物高剂量组（100　μg?kg^-1）大鼠较糖尿病模型组进食量明显降低（P< 0.01）,中剂量组（10 μg?kg^-1）、高剂量组（100 μg?kg^-1）大鼠较糖尿病模型组饮水量均明显减少（P<0.01）,各治疗组大鼠体重与糖尿病模型组比较差异均无显著性（P>0.05）；GLP-1类似物高剂量组（100 μg?kg^-1）、中剂量组（10 μg?kg^-1）大鼠空腹血糖(FPG)较糖尿病模型组均明显降低（P<0.01）；GLP-1类似物高剂量组(100 μg?kg^-1)大鼠血清TG较糖尿病模型组显著性降低（P<0.01）；GLP-1类似物中剂量组（10 μg?kg^-1）、GLP-1类似物高剂量组(100 μg?kg^-1)LDL较糖尿病模型组均明显降低（P<0.01）；GLP-1类似物中剂量组（10 μg?kg^-1）、高剂量组(100 μg?kg^-1)血清胰岛素和C肽水平较糖尿病模型组均显著升高（P<0.05）。结论：GLP-1类似物可以通过多种途径在治疗实验性糖尿病中发挥作用。

Therapeutic effects of GLP-1 analog on rats with experimental diabetes mellitus

Objective To investigate the therapeutic effects of glucagon-like peptide-1(GLP-1) analog on rats with experimental diabetes mellitus.Methods Eighty-four Wistar rats were divided randomly into normal control group,high fat forage group,low-dose GLP-1 analog group,middle-dose GLP-1 analog group,highdose GLP-1 analog group,diabetes mellitus model group and positive control group.Diabetes mellitus animal models were induced with high fat forage and injection of 40 mg·kg-1 STZ.After 7 and 14 d of GLP-1 analog therapy,the level of fasting plasma glucose(FPG) was detected with enzyme-chemical method.After 14 d of GLP1 analog therapy,the levels of serum total cholesterols(TC),triglyceride(TG),low-density lipoprotein(LDL) and high-density lipoprotein(HDL) were detected with enzyme-chemical method.The levels of serum insulin and C-peptide were measured with immunoradiometric assay method.Results After 14 d of GLP-1 analog injection,food intake in high-dose GLP-1 analog(100 μg·kg-1)group was less than that in DM group(P<0.01);Water intake in middle-dose GLP-1 analog(10 μg·kg-1) group and high dose(100 μg·kg-1)group were less than that in DM group(P<0.01).There were no statistical differences of body weight between all therapeutic groups and DM group(P<0.05).The levels of FPG in middle-dose GLP-1 analog(10 μg·kg-1 ) group and high dose(100 μg·kg-1)group were lower than that in DM group(P<0.01).The level of TG in high-dose GLP-1 analog(100 μg·kg-1)group was lower than that in DM group(P<0.01).The levels of LDL in middle-dose GLP1 analog(10 μg·kg-1) group and high dose(100 μg·kg-1)group were lower than that in DM group(P<0.01).The levels of serum insulin and C-peptide in middle-dose GLP-1 analog(10 μg·kg-1) group and high dose(100 μg·kg-1)group were higher than that in DM group(P<0.05).Conclusion GLP-1 analog can paly an important role in treatment of experimental diabetes mellitus through multiple ways.