激肽原酶对大脑中动脉缺血大鼠CGRP、RAMP1及VEGF表达的影响  

Effect of human urinary kallidinogenase on expression of CGRP,RAMP1 and VEGF in rats suffered focal cerebral ischemia

作　　者：常坤鹏 丁小灵[1] 王取南[2] 夏新[2] 

机构地区：[1]安徽医科大学附属省立医院神经内科,合肥230001 [2]安徽医科大学公共卫生学院卫生毒理系,合肥230032

出　　处：《安徽医科大学学报》2015年第8期1063-1067,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省年度重点科研项目(编号:1301043017)

摘　　要：目的研究激肽原酶预处理对脑缺血大鼠降钙素基因相关肽(CGRP)、受体活性修饰蛋白1(RAMP1)及血管内皮生长因子(VEGF)表达的影响。方法将80只大鼠随机均分成4组,假手术组(S组)、脑缺血组(I组)、激肽原酶低剂量组(3.75×10-3PNA单位/(kg·d),I+Kal1组)、激肽原酶高剂量组(17.25×10-3PNA单位/(kg·d),I+Kal2组)。经尾静脉注射给药1周后,采用线栓法堵塞大鼠右侧大脑中动脉,建立右侧大脑中动脉缺血模型。术后24 h红四氮唑法测量脑梗死体积,使用免疫组化和Western blot法观察CGRP蛋白在海马组织内的表达及RAMP1和VEGF蛋白在皮层组织内的表达。结果与S组相比,I组大鼠脑组织CGRP、RAMP1及VEGF蛋白水平表达增加(P<0.01);与I组相比,激肽原酶高、低剂量能明显促进脑缺血大鼠脑组织CGRP、RAMP1及VEGF蛋白的表达(P<0.05),脑梗死体积缩小(P<0.05)。结论激肽原酶促进缺血脑组织内CGRP、RAMP1蛋白的表达,CGRP、RAMP1的表达可能与脑梗死后血管新生有相关性。Objective To study the effect of human urinary kallidinogenase on expression of CGRP,RAMP1 and VEGF in rats suffered focal cerebral ischemia. Methods 80 male SD rats were randomly divided into four groups：sham operation group （S group）, ischemia group （I group）, low dose of kallidinogenase （3. 75 × 10 - 3 PNA / （kg ·d）, I ＋ Kal1 group） and high dose of kallidinogenase （17. 25 × 10 - 3 PNA/ （kg·d）,I ＋ Kal2 group）. Each group had 20 rats. The method of line bolt blocks the right middle cerebral artery in rats was used to establish the right MCAO ischemia model after tail intravenous dosing 1 week. TTC method was used to measure the cerebral in-farction volume. Immunohistochemistry and Western blot were used to evaluate the expression of CGRP protein in the hippocampus and the expression of RAMP1 and VEGF protein in the cerebral cortex. Results Compared with the S group, the expression of CGRP,RAMP1 and VEGF increased significantly in the I group rats （P 〈 0. 01）. While, compared with the I group, kallidinogenase high and low dose group can significantly reduce cerebral in-farction and markedly increase the expression of CGRP, RAMP1 and VEGF induced in cerebral ischemia 24 h after MCAO（P 〈 0. 05）. Conclusion Human urinary kallidinogenase can promote the expression of CGRP and RAMP1 in ischemic brain tissues and this may be one of the mechanisms of promoting angiogenesis after cerebral infarction.

关 键 词：降钙素基因相关肽 受体活性修饰蛋白 1 血管内皮生长因子 激肽原酶 缺血性脑卒中 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]