胰岛素穴位缓释注射对SD大鼠不同时间降糖效应的影响

Hypoglycemic Effect of Acupoint Injection of Sustained-release Insulin at Different Times in SD Rats

目的观察胰岛素结合PVP缓释剂穴位注射对SD大鼠不同时间血糖值、血清胰岛素含量变化并分析其相关性。方法将144只SD雄性大鼠随机分为A组(单纯胰岛素穴注组)、B组(胰岛素穴注缓释组)和C组(对照组)。各组以40%葡萄糖(剂量为2.2 g/kg)灌胃1 h后,A组和B组进行足三里穴位注射,C组不予处理。3组分别于穴位注射后0.5 h、3 h、6 h、8 h、10 h和24 h 6个时间点测定大鼠血糖值及血清胰岛素含量(C组按相应时点取血测定);同时在穴位注射后3 h、10 h、24 h3个时间点采用光镜观察各组大鼠足三里穴区组织刺激反应。结果 A组和B组降糖率均在穴位注射后3 h到达高峰后逐渐下降。A组在穴位注射后6 h降糖作用趋于稳定,B组在穴位注射后10 h趋于稳定,且B组在穴位注射后6 h与8 h的降糖作用明显优于A组(P<0.01)。A组血清胰岛素在穴位注射后3 h到达高峰(P<0.05),至6 h趋于稳定。B组在穴位注射后0.5 h、3 h、6 h、8 h 4个时间点血清胰岛素含量均显著低于A组(P<0.05)。大鼠血清胰岛素含量与降糖率相关性分析显示,A组存在显著正相关(P<0.01),B组存在低度正相关(P<0.05)。穴位注射后3h、8 h、24 h 3个时间点A组和B组大鼠足三里穴区周围肌纤维组织横纹清晰、结构完整,无明显变性、坏死和炎性反应,与C组比较无明显病理变化。结论 PVP缓释剂可减缓胰岛素在大鼠足三里穴区的吸收速率,同时延长了胰岛素降糖效应持续时间,而且显示血清胰岛素含量与降糖效应的相关性降低,提示穴位注射缓释技术可以延长药物穴位注射效应。

Objective To observe blood glucose values and serum insulin levels at different times after acupoint injection of insulin with PVP as a sustained release agent and analyze the correlation between them in SD Rats. Methods One hundred and forty-four male SD rats were randomized into groups A（acupoint injection of insulin alone）, B（acupoint injection of sustained-release insulin） and C（control）. At one hour after every group received an oral gavage of 40% glucose solution（2.2 g/kg）, groups A and B were given point Zusanli injection and group C was not treated. In the three groups of rats, blood glucose values and serum insulin levels were measured at six time points： 0.5, 3, 6, 8, 10 and 24 hours after acupoint injection（in group C at the corresponding time points）. In every group, the reaction of Point Zusanli region to the stimulation was observed by optical microscopy in at three time points： 3, 10 and 24 hours after acupoint injection. Results The glucose-lowering rate reached its peak at 3 hours after acupoint injection and then declined in groups A and B. The hypoglycemic effect tended to be stable at 6 hours after acupoint injection in group A and at 10 hours after acupoint injection in group B. The hypoglycemic effect was better in group B than in group A at 6 and 8 hours after acupoint injection（P〈0.01）. In group A, serum insulin reached its peak at 3 hours and tended to be stable at 6 hours after acupoint injection（P〈0.05）. Serum insulin levels were significantly lower in group B than in group A at four time pints： 0.5, 3, 6 and 8 hours after acupoint injection（P〈0.05）. An analysis of the correlation between rat serum insulin levels and the glucose-lowering rate showed a significant positive correlation in group A（P〈0.01） and a low positive correlation in group B（P〈0.05）. In groups A and B of rats, clear stripes and complete structure of muscle fibers were seen with no obvious degeneration, necrosis and inflammatory reaction around point Zusanli at three time points： 3, 8 and 24 hours after acupoint injection; there were no obvious pathological changes compared with group C. Conclusions PVP as a sustained release agent can slow down the absorption rate of insulin in rat point Zusanli region. Meanwhile, it prolongs the continuous time of the hypoglycemic effect of insulin. There is a low correlation between serum insulin levels and the hypoglycemic effect, suggesting that acupoint injection with a sustained release agent can prolong the effect of acupoint injection of medicine.