降血钙素基因相关多肽对早期糖尿病小鼠心功能的保护作用

目的 探讨外源性降血钙素基因相关多肽(CGRP)对早期糖尿病心肌缺血的保护作用.方法 给ICR小鼠腹腔注射链脲霉素建立糖尿病模型,将糖尿病小鼠及正常小鼠随机分为4组,两组为糖尿病组,两组为对照组;把实验活体小鼠的心脏从胸腔取出后,挂在Langendorff上稳定30 min.用western blot及放免法分别测定Vanilloid(VRl)受体和心肌组织中CGRP的表达,在缺血/再灌注过程中用Madlab系统测定心脏功能,包括左室舒张末压(LVEDP)、左室发展压(LVDP)、心率(HR)、冠状动脉流量(CF).将心脏流出的灌流液收集起来用ELISA试剂盒测定乳酸脱氢酶(LDH)的浓度.结果 2周后糖尿病心脏中VR1、CGRP的表达低于正常心脏(P＜0.01).与正常心脏相比,糖尿病心脏的LVEDP、CF更高(P＜0.05),而LVDP、HR更低(P＜0.05),但释放的LDH却低于正常心脏(P＜0.05).结论 糖尿病损害了心肌组织中CGRP的表达,外源性CGRP对早期糖尿病心脏心功能有更强的保护作用.

The Protective effect of CGPR on cardiac function in the early-staged diabetic mice postiscbemic injury

Objective Diabetic mice models were established.Hearts were separated from the body,reperfused after ischemia,and disposed of with the extraneous calcitonin gene-ralated peptide (CGRP),to prove if the CGRP had protective effect on the early-staged diabetic mice with cardiac ischemia.Method ICR mice were injected with Streptozocins intraperitoneally to establish diabetic model.The model mice and the normal mice were randomly divided into 4 groups:two diabetic groups,two control groups.Hearts of the experimental mice were taken out from the chest cavity alive,and hanged on the Langendorff steadily for 30min.Western blot and radioimmunoassay techniques were used to test expression of Vanilloid receptor(VR1) and CGRP in myocardic tissue;Madlab system was used to test the cardiac function,which including left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),heart rate (HR),and coronary artery flow (CF),in the process of ischemic reperfusion,And ELISA assay kit was used to measure the concentration of the lactate dehydrogenase (LDH) in perfusion fluid collected from the heart.Result Expressions of VR1 and CGRP in diabetic hearts were significantly lower than those in normal ones 2 weeks later(P＜0.01).By comparing with normal hearts,diabetic hearts had higher LVEDP and CF (P＜0.05),and lower LVDP and HR(P＜0.05).However,release of LDH were lower than normal ones (P＜0.05).Predisposition of normal and diabetic hearts with CGRP can improve the cardiac function after ischemie injury.And the beneficial effect was more profound in early-staged diabetic hearts than in normal ones.Conclusion The diabetes disease(DM) can impair the expression of CGRP in myocardiac tissue.The extraneous CGRP may exert more potent protective effect on cardiac function in the early-staged diabetic heart.