格列美脲新制剂对2型糖尿病大鼠血糖的影响

Effect of a new Glimepiride on blood glucose in type 2 diabetic rats

目的探讨格列美脲新制剂对2型糖尿病大鼠血糖的影响。方法用高分子聚合物聚己内酯合成载体,加入格列美脲原药制成可皮下埋植的缓释降糖制剂。将24只雄性SD大鼠随机分为空白载体组、格列美脲灌胃组(Gli)、皮下埋植格列美脲缓释剂组(GSR)及正常对照组,每组6只。通过高脂高糖饲料喂养和腹腔注射小剂量链脲菌素(STZ)30 mg/kg,建立2型糖尿病(T2DM)大鼠模型,将空白载体、格列美脲缓释制剂分别植入两组大鼠的颈背部皮下,药物灌胃组予格列美脲溶液灌胃,正常对照组大鼠予同体积的蒸馏水灌胃。干预期间,采集各组大鼠血样检测生化指标,包括空腹血糖、餐后2 h血糖、糖化血红蛋白、谷草转氨酶(AST)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(CRE)及血药浓度,共干预12周。结果GSR组在给药第9周空腹血糖低于空白载体组,差异有统计学意义(P<0.05);第5周餐后2 h血糖低于空白载体组,差异有统计学意义(P<0.05),疗效均持续至实验结束。GSR组给药第9周空腹血糖低于Gli组,差异有统计学意义(P<0.05),第5周餐后2 h血糖低于Gli组,差异有统计学意义(P<0.05)。实验结束时,GSR组与Gli组糖化血红蛋白均低于空白载体组,差异有统计学意义(P<0.05),但GSR组与Gli组糖化血红蛋白差异无统计学意义(P>0.05)。干预12周后,两组间ALT、AST、CRE水平的差异无统计学意义(P>0.05),GSR组的BUN低于Gli组,差异有统计学意义(P<0.05)。整个实验过程中,Gli组血药浓度高于GSR组,差异有统计学意义(P<0.05)。结论皮下埋植格列美脲新制剂,用药1次,可稳定降糖长达12周,血药浓度稳定,对肾功能的损伤更小。

Objective To investigate the effect of a new Glimepiride on blood glucose in type 2 diabetic rats.Methods Twenty-four healthy male SD rats were randomly divided into blank carrier group,glibenclamide(Gli)group,glibenclamide sustained-released(GSR)group and healthy control group.Except for the healthy control group,the type 2 diabetes mellitus model was established by high fat,high-sugar diet and intraperitoneal injection of streptozotocin(STZ)at 30mg/kg.The blank carrier and the Glimepiride sustained-release preparation were implanted subcutaneously into the neck and back of the two groups seperately.The Glimepiride solution was perfused into the stomach of the Gli group,and the same volume of distilled water was perfused into the stomach of the healthy control group.During the intervention,blood samples were collected for biochemical parameters including serum levels of fasting blood glucose,2 h postprandial blood glucose,glycosylated hemoglobin,alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)and blood drug concentration,total intervention for 12 weeks.Results The fasting blood glucose of GSR group was lower than that of blank carrier group at the 9th week,the difference was statistically significant(P<0.05).The postprandial 2 h blood glucose was lower than that of the blank carrier group from the 5th week,the difference was statistically significant(P<0.05),and the therapeutic effect lasted until the end of the experiment.The fasting blood glucose of the GSR group was lower than that of the Gli group from the 9th week,the difference was statistically significant(P<0.05).The 2 h postprandial blood glucose of the GSR group was lower than that of the Gli group from the 5th week,the difference was statistically significant(P<0.05).At the end of the experiment,the glycosylated hemoglobin of GSR group and Gli group were lower than that of blank carrier group,the difference was statistically significant(P<0.05).The glycosylated hemoglobin of GSR group and Gli group were not significantly different(P>0.05).After 12 weeks of intervention,there was no significant difference in ALT,AST and CRE levels between the two groups(P>0.05),blood urea nitrogen in GSR group was lower than that in Gli group,the difference was statistically significant(P<0.05).During the whole experiment,the serum concentration of Gli group was higher than that of GSR group,the difference was statistically significant(P<0.05).Conclusion Subcutaneous implantation of a new Glimepiride,once medication,can be stable for 12 weeks,blood drug concentration is more stable,kidney function damage is less.