胰岛素不同给药途径控制2型糖尿病小鼠血糖的药效动力学研究

Study on the pharmacodynamics of different administration methods of insulin on type Ⅱ diabetes model

目的:观察胰岛素皮下(s.c.)、腹腔(i.p.)注射两种给药途径对2型糖尿病小鼠血糖的影响。方法:采用空腹血糖高于20.0 mmol/L的雄性Kk小鼠作为2型糖尿病模型,分为s.c.组(n=6)和i.p.组(n=6),分别s.c.和i.p.不同剂量的胰岛素,一次给药后尾静脉测血糖,连续监测2 h。结果:非禁食状态下,s.c.和i.p.组注射胰岛素前血糖分别为(32.0±1.5)、(31.0±1.5)mmol/L,注射胰岛素后血糖逐渐下降。胰岛素剂量不足时,血糖30 min时达最低点,随后逐渐上升;胰岛素适量时,血糖30 min时达正常水平,维持一定时间后逐渐上升;胰岛素剂量过高时,血糖30 min时低于正常水平,并且持续缓慢降低。以30 min时的血糖值为药效指标,做剂量-效应关系曲线,胰岛素剂量在1.1～1.7 U/kg范围时,i.p.组血糖可稳定地控制在正常水平(5.1±0.2)mmol/L,曲线形成显著的平台;s.c.组的血糖则在2.1～9.2 mmol/L之间,与剂量-效应曲线呈线性关系。对于本组实验,腹腔胰岛素给药的有效剂量范围为皮下给药最适剂量的±21%。结论:胰岛素腹腔给药较皮下给药控制血糖更为平稳,血糖波动小,不易造成低血糖。

AIM： To observe the effects of subcutaneous and intraperitoneal injection for insulin on the rats with Type Ⅱ diabetes. METHODS： Kk mice with fasting blood sugar level higher than 20 mmol/L was set as Type II diabetes model and divided into subcutaneous injection group （s.c. group, n = 6）and intraperitoneal injection group （i. p. group, n = 6） with different dosis of insulin, and the tail blood sugar levels were monitored for two continuous hours after administration. RESULTS： Under non-fasting condition, the blood sugar levels of s.c. group and i.p. group were （32.0±1.5）, （31.0±1.5） mmol/L, respectively before insulin injection, and were decreased gradually after injecting. When insulin dose was not sufficient, the blood sugar level was at the bottom at the 30th minutes, and then went upwards gradually. When the dose was appropriate, the blood sugar level was at normal level at the 30th minutes, and then went upwards gradually after maintaining a certain time. When insulin was overdose, the blood sugar level was below normal level and decreased gradually and slowly. The dose-response curve was drawn according to the blood sugar level at the point of 30 minutes. When the insulin dose was in the range of 1.1 - 1.7 U/kg, the blood sugar level could be stably controlled within normal scope（5.1±0.2） mmol/L in i.p. group, and the dose-response curve showed an obvious plateau phase. The dose-response curve showed a linear relation with the blood sugar level in the range of 2.1 - 9.2 mmol/L in s.c. group. The effective dose scope of insulin intraperitoneal injection was ＋ 21% of the subcutaneous injection dose. CONCLUSION： Compared with subcutaneous injection, ntraperitoneal injection can control blood sugar level more stably, cause less fluctuation and a lower chance of hypoglycemia.