降钙素基因相关肽对早期糖尿病大鼠血管ATP敏感性钾通道的影响

Effects of calcitonin gene related peptide on ATP-sensitive potassium channels of blood vessels in short-term diabetes rats

目的 研究早期糖尿病大鼠血管平滑肌ATP敏感性钾通道 (KATP)的变化 ,进一步探讨糖尿病血管功能的改变机制。方法 大鼠单次注射链佐霉素6 0mg·kg- 1制作糖尿病模型 ;1周或 2周后 ,两步酶消化法进行肠系膜动脉平滑肌细胞 (MASMC)的消化分离 ;全细胞膜片钳制技术记录MASMC的ATP敏感性钾电流 (IKATP)。结果 在保持电位 - 40mV ,指令电位 +5 0mV时 ,对照组 ,糖尿病 1周和 2周组MASMC的IKATP 分别为 (79± 6 ) ,(70± 7)和(4 8± 9)pA·pF- 1,糖尿病 2周组的IKATP明显低于对照组。给予降钙素基因相关肽 0 .0 1～ 10 0nmol·L- 1,3个组的IKATP 均浓度依赖性增加 ,对照组 :Y =118.3+2 .9X ,r =0 .887;糖尿病 1周组 :Y =12 3+4.4X ,r =0 .981;糖尿病 2周组 :Y =10 0 .2 +4.6X ,r =0 .975 ;糖尿病组IKATP对降钙素基因相关肽量效反应斜率高于对照组。结论 早期糖尿病血管平滑肌的基础IKATP减小 ,IKATP对降钙素基因相关肽的量效反应斜率增加。

AIM To explore the mechanism of functional change in blood vessels of diabetes rats with respect to ATP sensitive potassium channel(K ATP ). METHODS The diabetes rat model was made by single injection of streptozotocin (60 mg·kg -1 , ip). The mesentery artery smooth muscle cells (MASMC) were obtained 1 or 2 weeks later by two step enzyme digestion method, and the current of K ATP (I KATP ) was recorded by whole cell patch clamp technique. RESULTS When holding potential was -40 mV, commanding potential was +50 mV, the I KATP recorded were (79±6), (70±7) and (48±9)pA·pF -1 in control, 1 week diabetes and 2 week diabetes groups, respectively. And I KATP in 2 week diabetes group was lower than that in control significantly. I KATP in three groups increased concentration dependently when concentration of calcitonin gene related peptide (CGRP) increased from 0.01 to 100 nmol·L -1 : control: Y=118.3+2.9X, r=0.887; 1 week diabetes group: Y=123+ 4.4X , r=0.981; 2 week diabetes group: Y= 100.2 +4.6X, r=0.975. The slopes of concentration response curve in diabetes groups were higher than that in control. CONCLUSION The basic I KATP in MASMC of short term diabetes rats attenuated, but the slopes of concentration response curves of CGRP in diabetes groups were higher than that in control.