胰岛素及其受体在肾缺血再灌注损伤中的作用  

Study on the Insulin and Insulin Receptor in the Progression of Renal Ischemic and Reperfusion

作　　者：何涛[1] 李蓉晖[2] 甘淋[3] 杨烨[1] 刘佳佳[3] 陈曼玲[2] 

机构地区：[1]泸州医学院基础部生物化学教研室,泸州646000 [2]四川大学华西基础医学与法医学院生物化学教研室 [3]泸州医学院分子生物学实验室

出　　处：《四川大学学报（医学版）》2003年第4期660-662,共3页Journal of Sichuan University(Medical Sciences)

基　　金：四川省教育厅自然科学重点项目 (川教计 14 3号 )资助

摘　　要：目的　探讨肾缺血再灌注 (IR)过程中胰岛素及其受体的作用。方法　采用钳夹肾动脉的方法建造急性缺血再灌注肾损伤模型。将大耳白兔分为对照组、单纯缺血再灌注组 (IR组 )、胰岛素处理组 (Ins+IR组 ) 3组 ,Ins+IR组再灌注的同时给予胰岛素溶液 (Ins3U/ kg.wt) ,而对照组和 IR组则给予等量生理盐水。测定各组动物的血糖、血清胰岛素水平及肾组织胰岛素受体高、低亲和力常数 (Kd1 ,Kd2 )和高、低亲和力受体最大结合容量(Bmax1 ,Bmax2 )。结果　缺血再灌注 2 h后 ,3组动物血糖值、血清胰岛素水平均较术前显著升高 (P<0 .0 5 ) ,IR组尤为显著 ,IR组 Kd1 、Kd2 、Bmax1 、Bmax2 均较对照组显著降低 (P<0 .0 5 ) ,Ins+IR组仅 Bmax2 较对照组显著降低 (P<0 .0 5 ) ;4 8h后 ,3组动物血糖值恢复至正常水平 ,对照组胰岛素水平恢复至正常水平 ,IR组也较 2 h时明显下降(P<0 .0 5 ) ,但仍明显高于对照组 (P<0 .0 5 ) ,3组动物 Kd1 、Bmax1 值无差异 ,Ins+IR组 Bmax2 仍维持较低水平 (P<0 .0 5 ) ,Ins组 Kd2 明显高于对照组 (P<0 .0 5 )。结论　在肾 IR过程中 ,内源性胰岛素的作用减弱 ,外源性胰岛素对肾组织高亲和力受体位点无下降调节作用 ,但胰岛素可引起低亲和力受体数目的下调。胰岛素减轻 IR肾损伤的作用主要是?Objective To evaluate the effect of insulin and it's receptor on the kidney of rabbit with acute ischemic/reperfusion injury. Methods Twenty three Japanese white rabbits were allocated randomly into the control group, ischemic/reperfusion group(IR group), and insulin treatment group(Ins IR group). The IR group received clamping for 1 h followed by 2 h or 48 h of reperfusion. In the Ins IR group, insulin injection (Ins 3U/kg, glucose 1.5 g/kg,K + 4 mg/kg,Mg 2+ 1 7 mg/kg) was administered intravenously twice a day for two days, whereas only normal saline in equal amount was given to the IR group and control group. At 2 h or 48 h after reperfusion, glucose and insulin in serum were determined. Rough plasma of renal tissue was prepared by repeated centrifugation. Insulin receptor in renal tissue was analyzed by radioligand binding assay. The binding data were calculated according to Scatchard using the ligand program. Statistical significance was analyzed with the paired t test. Results The level of blood glucose increased after 2 h reperfusion in three groups, but the level in IR group increased much higher than those in control and Ins IR groups( P <0.05). The level of serum insulin of IR group after 2 h reperfusion was significantly higher than that of control ( P <0.05). Scatchard analysis showed curvilinear profiles, indicating that there are two classes of receptors with different affinity or the presence of a single class of receptors with a negative cooperative hormone receptor interaction. Data analyzed by a two site model showed that the values of Bmax 1(high affinity site), Bmax 2(low affinity site) and Kd 1, Kd 2 after 2 h reperfusion were significantly lower than those of control ( P <0.05). In IR Ins group, only Bmax 2 decreased ( P <0.05, compared with control). 48 h after IR there was no difference in Bmax 1, Kd 1 between the 3 groups, but Bmax 2 of IR Ins group was still lower than that of control ( P <0.001) and IR group( P <0.05). The Kd 2 of IR group increas

关 键 词：胰岛素 胰岛素受体 缺血再灌注 肾损伤 

分 类 号：R692.9[医药卫生—泌尿科学]