大黄酸治疗对db/db小鼠第1相胰岛素分泌的影响

Effect of rhein treatment on first-phase insulin secretory function in db/db mice

目的:通过db/db小鼠先天性2型糖尿病动物模型,探讨大黄酸对胰岛β细胞第1相胰岛素分泌功能的影响。方法:20只4周龄db/db雄性小鼠,随机分成治疗组和对照组,每组10只。另取10只db/m雄性小鼠作为非糖尿病正常对照。治疗组每日固定时间给予大黄酸120 mg.kg-1灌胃,db/db对照组和db/m对照组均给予相同体积的1%纤维素钠,连续给药8周,测定给药前后小鼠体重和空腹血糖,并于给药结束后分离胰岛,建立离体胰岛灌流系统,开始2.8 mmol.L-1KRB0.5 mL.h-1速度灌流1 h,后换为16.7 mmol.L-1KRB 1 mL.h-1灌流,在-30,-20,-10,0,1/3,2/3,1,4/3,5/3,2,3,4,5,6,7,8,9,10,15,20,30 min时分别收集灌流出的液体,-80℃保存后测定胰岛素。结果:db/db大黄酸治疗组和对照组相比,空腹血糖明显下降。db/db对照组小鼠的离体胰岛第1相胰岛素分泌明显受损,而db/db大黄酸治疗组小鼠离体胰岛在高糖刺激后立即出现明显的第1相胰岛素分泌高峰,较db/db明显好转。结论:早期大黄酸治疗可以明显改善db/db小鼠的葡萄糖耐量,恢复第1相胰岛素分泌功能,保护胰岛功能。

Objective： The aim of the present study is to investigate the effect of rhein treatment on the first-phase insulin secretory function in db/db mice.Method： Twenty 4-week-old male db/db mice were randomized to treatment with rhein（120 mg·kg^-1,n=10） and placebo respectively（1% natrium cellulose solution,n=10） by gavage for 8 weeks respectively.Ten age-matched non-diabetic male littermates db/m mice treated with placebo were studied as non-diabetic control.Body weight and fasting blood glucose level were measured before and after medication.The islets were isolated after 8 weeks＇ gavage.Islet perifusion system was set up,and all columns were perfused in parallel at a flow rate of 0.5 mL·min-1 with KRB（2.8 mmol·L^-1 glucose） at 37 ℃.After 60-min static incubation with KRB（2.8 mmol·L^-1 glucose）,the islets were stimulated in the continuous presence of a high concentration of 16.7 mmol·L^-1 glucose.Samples were collected every 20-second until 2-min,every 1-min until 5-min,thereafter every 5-min until 30-min.Samples were immediately stocked at-80 ℃ until further analysis.Result： Compared with the db/db control group,the fasting glucose concentration was significantly decreased in the rhein treatment group.The first-phase insulin secretory function was impaired significantly in db/db mice,while the first-phase insulin secretory peak was obvious in the rhein treatment mice.Conclusion： Rhein treatment significantly improved glucose tolerance,restored the first-phase insulin secretion and protected the islets function.