他克莫司对大鼠血糖的影响及其作用机制

目的 观察不同浓度的他克莫司对大鼠血糖的影响.方法 选取雄性SD大鼠30只,体重70～85g,随机等分为三组.A组大鼠为他克莫司加五脂胶囊组,每日给予他克莫司(普乐可复Astellas Ireland Co.,Ltd生产)2 mg/kg和五酯软胶囊(四川光大制药有限公司生产)0.2粒/kg;B组为他克莫司组,每日给予他克莫司2 mg/kg；C组为对照组,每日给予同等量生理盐水,三组大鼠均在空腹时灌胃给药,用药1h后喂食.用药时间为5个月.每月监测大鼠他克莫司血药浓度和空腹血糖.结果 在用药的1～5个月期间,A组大鼠他克莫司血药浓度均明显高于B组.在用药的第1个月和第2个月,三组大鼠空腹血糖无明显差异(P＞0.05),用药第3个月后,A、B两组大鼠血糖均明显高于对照组(P＜0.01),A组大鼠血糖略高于B组,二者之间差异并无统计学意义(P＞0.05)；用药第4、5个月后A、B两组大鼠的血糖持续升高,并且A组大鼠血糖明显高于B组(P＜0.01)；A组的胰岛素分泌指数和敏感指数均明显低于C组(P＜0.01).结论 他克莫司通过减少胰岛素的分泌、增加胰岛素抵抗导致大鼠血糖升高,这种升血糖作用呈时间依赖性和浓度依赖性.

Effect of tacrolimus on the blood glucose in rats and its mechanism

Objective To observe the effect of tacrolimus at different concentrations on the blood glucose in rats.Methods 30 male SD rats,weighing about 80 g,were randomly divided into three groups.Group A was given tacrolimus（Astellas Ireland Co.,Ltd） 2 mg/kg per day and Wu Zhi soft capsules containing schizandrin A and other components（Sichuan Guangda Pharmaceutical Co.,Ltd.） 0.2 / kg per day for 5 months.Group B was given tacrolimus 2 mg/kg per day for 5 months.Group C was used as control and received daily saline solution.The three groups of rats were administered orally in the fasting state.The tacrolimus plasma concentration and fasting blood glucose were monitored monthly.Results Blood concentration of tacrolimus of group A was significantly higher than that in the group B（P 0.01）.In the first two months of drug administration,there was no significant difference in fasting blood glucose among the three groups（P 0.05）.The Groups A and B had significantly higher blood glucose than in the group C three months after treatment（P 0.01）.In the last two months the blood glucose of the groups A and B continued to rise,and the blood glucose in group A was significantly higher than that in group B（P 0.01）.Conclusions Tacrolimus causes elevated blood glucose by reducing insulin secretion and increasing insulin resistance.This glycemic effect is time-dependent and dose-dependent.