黄芩素对2型糖尿病小鼠GLP-1及胰高血糖素分泌的影响

Effects of baicalin on GLP-1 and glucagon secretion in type 2 diabetic mice

目的探讨黄芩素对2型糖尿病模型小鼠胰高血糖素样肽-1(GLP-1)及胰高血糖素分泌的影响。方法40只8周龄C57BL/6J小鼠适应性饲养1周后,选取30只小鼠给予高脂饲料喂养和链脲佐菌素(STZ)一次性注射,均成功建立2型糖尿病小鼠模型,并随机分为模型组(生理盐水灌胃)、二甲双胍组(二甲双胍0.30 g/kg灌胃)和黄芩素组(黄芩素250 mg/kg灌胃),每组各10只。以正常饲料喂养的10只小鼠为正常对照组(正常组,生理盐水灌胃)。各组连续灌胃给药6周。分别于给药前和给药后采集尾尖静脉血,检测空腹血糖(FBG)、餐后2 h血糖值(2 h PBG),酶联免疫吸附实验检测空腹胰岛素、胰高血糖素和GLP-1水平,qRT-PCR检测给药后小鼠回肠组织中胰高血糖素原(PG)和前激素转化酶(PC1/3)mRNA表达,给药结束后行腹腔注射葡萄糖耐量实验评估胰高血糖素分泌功能。结果给药前,与正常组比较,模型组、二甲双胍组和黄芩素组FBG和2 h PBG均显著升高,胰岛素水平显著降低,胰高血糖素水平显著升高,血清中GLP-1水平显著降低(均P<0.05);给药后,与模型组比较,二甲双胍组和黄芩素组FBG和2 h PBG均显著降低,胰岛素水平显著升高,胰高血糖素水平显著降低,血清中GLP-1水平显著升高(均P<0.05);给药后,与正常组比较,模型组小鼠回肠组织中PC1/3 mRNA相对表达量显著下降,与模型组比较,二甲双胍组和黄芩素组小鼠回肠组织中PG、PC1/3 mRNA相对表达量均明显上升(均P<0.05);在葡萄糖注射后0、30、60和120 min,模型组血糖和胰高血糖素均显著高于正常组,二甲双胍组和黄芩素组血糖和胰高血糖素均显著低于模型组(均P<0.05)。结论黄芩素可降低2型糖尿病小鼠血糖和胰高血糖素水平,提高血清GLP-1水平,促进肠道GLP-1的合成。

Objective To determine the effect of baicalin on glucagon-like peptide-1(GLP-1)and glucagon secretion in type 2 diabetes model rats.Methods After 1 weeks of adaptive feeding,40 C57BL/6J 8 week old mice were fed with high-fat diet and single dose injection of streptozotocin(STZ)for 1 weeks.The mice with type 2 diabetes were successfully established and randomly divided into model group(normal saline,gastric lavage),metformin group(two metformin 0,30 g/kg gavage)and baicalein group(baicalein 250 mg/kg gavage),10 rats in each group.Ten mice fed with normal diet were used as the normal control group(normal group,intragastric administration of normal saline).Each group was administered by gavage for 6 weeks.The blood of caudal cusp vein was collected before and after administration to detect fasting blood glucose(FBG)and 2h postprandial blood glucose(2H PBG).The levels of fasting insulin,glucagon and GLP1 were detected by enzyme-linked immunosorbent assay.The mRNA expressions of glucagon(PG)and prohormone converting enzyme(PC1/3)in mouse ileum were detected by QRT PCR,After administration,the glucagon secretion function was evaluated by intraperitoneal injection glucose tolerance test.Results Before administration,compared with the normal group,FBG and 2H PBG in model group,metformin group and baicalein group increased significantly,insulin level decreased significantly,glucagon level increased significantly,and serum GLP 1 level decreased significantly(all P<0.05).After administration,compared with the model group,FBG and 2H PBG in metformin group and baicalein group decreased significantly,insulin level increased significantly,glucagon level decreased significantly,and serum GLP1 level increased significantly(all P<0.05).After administration,compared with the normal group,the relative expression of PC1/3 mRNA in the ileum of mice in the model group decreased significantly.Compared with the model group,the relative expression of PG and PC1/3 mRNA in the ileum of mice in metformin group and baicalein group increased significantly(all P<0.05).At 0,30,60 and 120 min after glucose injection,the blood glucose and glucagon in the model group were significantly higher than those in the normal group,and the blood glucose and glucagon in the metformin group and baicalein group were significantly lower than those in the model group(all P<0.05).Conclusion Baicalin could reduce blood glucose and glucagon levels in type 2 diabetic mice,increase serum GLP-1 level,and promote intestinal GLP-1 synthesis.