健脾法择时给药对实验性糖尿病小鼠血糖昼夜节律的影响

Effect of the Time-choosing Administration of Spleen-reinforcing Therapy on the Blood Glucose Level and Circadian Rhythm in Experimental Diabetic Mice

目的观察健脾法择时给药对实验性糖尿病小鼠血糖昼夜节律的影响。方法采用四氧嘧啶(ALX)200mg/kg腹腔注射制作小鼠糖尿病模型,将糖尿病模型小鼠随机分为3组,分别于6am、6pm给予健脾方水煎剂和等量生理盐水灌胃,并设立正常对照组,各组分别于给药前1d、给药1w、给药2w测定昼夜6个时间点的血糖值,描绘各组昼夜血糖-时间曲线图。对各组动物血糖值的生物时间序列进行宏观分析并比较。结果正常小鼠昼夜血糖浓度的波动呈明显的峰值与谷值交替,在所检测的24h之内,出现两次峰值(时间分别为10am和10pm)和两次谷值(时间分别为6am和6pm),且昼夜血糖浓度均低于10.0mmol/L。糖尿病小鼠血糖水平的昼夜节律与正常小鼠相比,其峰值与谷值时间发生移位,出现明显的节律紊乱,其血糖浓度也有两次峰值时间(分别为10am和2am)、两次谷值时间(分别为2pm和6am),且其血糖浓度明显高于10.0mmol/L,但糖尿病小鼠的血糖峰值浓度与谷值浓度相比无统计学差异(P>0.05)。糖尿病小鼠给药2w后血糖水平均有所下降,而给予生理盐水对糖尿病小鼠血糖无明显影响;不同时间给药对糖尿病小鼠血糖昼夜节律均有一定的调整作用,6am给药使血糖的昼夜节律恢复得更为理想。结论健脾法能够降低糖尿病小鼠血糖浓度,而且随着给药时间的延长其作用更加明显;不同时间给药对糖尿病小鼠血糖水平的昼夜节律具有不同的影响,健脾法存在择时给药的问题。

Objective To study the effect of time-choosing administration of spleen-reinforcing therapy on the blood glucose level and its circadian rhythm of experimental diabetic mice. Methods Alloxan 200mg/kg was injected to establish the model of diabetes mellitus. All diabetic mice were randomly divided into three groups, and then given by gastric perfusion of Jianpi Recipe （Recipe to reinforce the spleen） at 6 am, 6 pm and normal saline respectively. The normal control group was set up for contrast. Bloodglucose concentration was examined every fourhours in all groups including normal mice at the day of pre-treatment, at the day after one-week treatment and at the day after two-week treatment. Bloodglucose-time diagrams were depicted respectively. All biological time-series of bloodglucose concentrations were analyzed with macroscopic analysis. Results The peak and valley of bloodglucose concentrations were alternatively presented in the normal mice. The circadian rhythm of normal bloodglucose concentrations was obvious and its peak concentrations presented in 10am and 10pm, its valley concentrations presented in 6 am and 6 pro. The normal bloodglucose concentrations were always under 10.0mmol/L. The bloodglucose concentrations of diabetic mice were obviously above 10. 0mml/L, and its circadian rhythm was obviously abnormal compared with the normal mice. The peak concentrations of the diabetic mice were presented in 10am and 2am, and its vallley concentrations presented in 2 pm and 6 am. There is not significant difference between the peak blood glucose and valley value in diabetic mice（P〉0. 05）. The two-week administration of Jianpi Recipe decreased the bloodglucose of diabetic mice. Normal saline had no obvious influence on it. Time：choosing recipe administration could adjust the circadian rhythm of bloodglucose concentration. Administration at 6am was more effective in adjusting bloodglucose rhythm. Conclusion Spleen-reinforcing therapy can decrease the bloodglucose of diabetic mice, and the effect tend to be more obvious with the administration prolonging. Administration at different time exerts different effect on circadian rhythm of bloodglucose concentrations. There exists different effect in different time administration in spleen-reinforcing therapy.