他克莫司对大鼠肝细胞膜胰岛素受体影响的研究

Effects of tacrolimus on insulin receptors in rat hepatocytic membrane

目的通过观察他克莫司(FK506)对大鼠肝细胞膜胰岛素受体(IR)的作用,以期探讨FK506对糖代谢影响的可能机制。方法雄性纯系SD大鼠按不同浓度的FK506[0.1、1、3mg/(kg·d)]分别灌胃给药,2周后处死大鼠取肝脏进行肝细胞膜受体结合反应,用放免法测定IR的结合能力。结果FK506处理组大鼠肝细胞膜高亲和力IR亲和常数(K1)及低亲和力IR亲和常数(K2)均无显著变化;高浓度[1、3mg/(kg·d)]处理组大鼠肝细胞膜高亲和力IR结合位点浓度(Q1)与对照组相比明显降低,低亲和力IR结合位点浓度(Q2)无明显变化,而低浓度[0.1mg/(kg·d)]处理组高、低亲和力IR结合位点浓度与对照组相比均无显著变化。结论高浓度FK506对大鼠肝细胞膜IR结合产生一定程度影响,提示这可能是FK506影响机体糖代谢的作用机制之一。

Objective To explore the effects of tacrolimus on insulin receptors in rat hepatocytic membrane and to document the possible metabolism of tacrolimus on glucose metabolism. Methods Tacrolimus was given through gastric tube with different doses of 0.1, 1.0 or 3.0 mg/（kg·d） for 2 weeks. The animals were sacrificed and the liver specimens were obtained and hepatocytic membrane was separated to measure the binding capacity of insulin receptor by radioimmunoassay technique, Results Affinity constant K1 and K2 of higher affinity receptor and lower affinity receptor did not change in three groups, but the binding sites concentration （Q1）of higher affinity receptor decreased and the binding sites concentration （Q2） of lower affinity receptor kept in normal range in the higher dose groups [ 1,3 mg/ （kg· d） ]. Conclusion Tacrolimus influenced the binding capacity of insulin receptor in rat hepatoeytic membrane, which might be another cause of hyperglycemia after tacrolimus usage.