尤瑞克林对大鼠缺血-再灌注后缓激肽受体B1和B2表达的影响  

Effect of urinary kallidinogenase on the expression of bradykinin receptor B1 and B2 after ischemia-reperfusion injury in rats

作　　者：孙洲[1] 向栩莹 晏桂林 陆观凤 杨燕泽 钟玉馨 张磊[1] Sun Zhou;Xiang Xuying;Yan Guilin;Lu Guanfeng;Yang Yanze;Zhong Yuxing;Zhang Lei(Department of Neurology,Union Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430021,China;不详)

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430021 [2]武汉市普爱医院神经内科

出　　处：《中国脑血管病杂志》2019年第12期653-657,共5页Chinese Journal of Cerebrovascular Diseases

基　　金：天普凯力康研究基金(KF201204)

摘　　要：目的观察不同剂量尤瑞克林对大脑中动脉闭塞(MCAO)的缺血-再灌注(I/R)SD大鼠缓激肽受体B1(B1R)、缓激肽受体B2(B2R)表达的影响。方法应用改良后Zea Longa线栓方法建立SD大鼠右侧MCAO模型,缺血2 h时拔栓模拟缺血-再灌注,将制备成功的25只SD大鼠按随机抽样法分为假手术组、I/R模型组(I/R+等渗盐水组)、尤瑞克林低剂量治疗组(I/R+LDP组)、尤瑞克林中等剂量治疗组(I/R+MDP组)、尤瑞克林高剂量治疗组(I/R+HDP组),每组5只,术后30 min首次给予尤瑞克林(I/R+LDP组:3.50×10-3 PNAU/kg;I/R+MDP组:8.75×10-3 PNAU/kg;I/R+HDP组:17.50×10-3 PNAU/kg)或等渗盐水尾静脉注射,连续注射7 d、每日定时注射1次,7 d后取材,运用实时定量反转录聚合酶链反应(RT-PCR)检测梗死灶边缘区域B1R、B2R的mRNA相对表达水平,血管性血友病因子(vWF)免疫荧光测定梗死边界区域微血管密度。结果(1)B1R mRNA表达:与I/R+等渗盐水组比较,I/R+LDP组、I/R+MDP组、I/R+HDP组B1R的mRNA表达水平均上调[(0.34±0.05)、(0.35±0.04)、(0.47±0.03)比(0.23±0.05),均P<0.05];与I/R+LDP组及I/R+MDP组比较,I/R+HDP组B1R的mRNA表达水平均上调(均P<0.05)。(2)B2R mRNA表达:与假手术组比较,I/R+等渗盐水组B2R的mRNA表达水平上调[(0.33±0.01)比(0.23±0.02),P<0.05]。与I/R+等渗盐水组比较,I/R+LDP组、I/R+MDP组、I/R+HDP组B2R的mRNA表达水平均上调[分别为(0.49±0.02)、(0.52±0.04)、(0.71±0.03),均P<0.05];与I/R+LDP组及I/R+MDP组比较,I/R+HDP组B2R的mRNA表达水平均上调(均P<0.05)。(3)微血管密度:与假手术组比较,I/R+等渗盐水组的微血管计数明显增多[(169±6)比(74±12),P<0.01];与I/R+等渗盐水组比较,I/R+LDP组、I/R+MDP组、I/R+HDP组的微血管计数均明显增多[分别为(240±9)、(252±9)、(349±17),均P<0.01];与I/R+LDP组及I/R+MDP组比较,I/R+HDP组微血管计数均明显增多(均P<0.01)。结论一定剂量的尤瑞克林上调MCAO大鼠B1R、B2R表达,发挥促血管再生的作用,�Objective To observe the effects of different doses of human urinary Kallidinogenase(HUK)on the expression of bradykinin 1 receptor(B1R)and bradykinin 2 receptor(B2R)in SD rats with middle cerebral artery occlusion(MCAO).Methods The right MCAO model of SD rats was established by modified Zea Longa thread thrombus method.The 25 successfully prepared SD rats were randomly divided into five groups(5 in each group):the Sham group,the I/R model group(I/R+saline group),the HUK low dose treatment group(I/R+LDP group),the HUK medium dose treatment group(I/R+MDP group)and the HUK high dose treatment group(I/R+HDP group).After 30 min,each group was given HUK(the I/R+LDP group:3.50×10-3 PNAU/kg;the I/R+MDP group:8.75×10-3 PNAU/kg;the I/R+HDP group:17.50×10-3 PNAU/kg)or saline tail vein injection for continuous 7 days.The samples were taken after regular injection once a day.The relative expression of mRNA in the marginal area of infarction was detected by real-time quantitative reverse transcription-polymerase chain reaction(RT-PCR),and microvascular growth density(MVD)was measured by vWF factor immuno-fluorescence(FITC).Results(1)B1R mRNA expression:Compared with I/R+saline group,the mRNA expression of B1R in I/R+LDP group,I/R+MDP group,I/R+HDP group was all up-regulated([0.34±0.05],[0.35±0.04],[0.47±0.03]vs.[0.23±0.05],all P<0.05);Compared with I/R+LDP group and I/R+MDP group,the mRNA expression of B1R in I/R+HDP group was was all up-regulated(all P<0.05).(2)B2R mRNA expression:Compared with Sham group,the mRNA expression of B2R in I/R+saline group was up-regulated([0.33±0.01]vs.[0.23±0.02],P<0.05);Compared with I/R+saline group,the mRNA expression of B2R in I/R+LDP group,I/R+MDP group,I/R+HDP group was all up-regulated([0.49±0.02],[0.52±0.04],[0.71±0.03],respectively,all P<0.05);Compared with I/R+LDP group and I/R+MDP group,the mRNA expression of B2R in I/R+HDP group was was all up-regulated(all P<0.05).(3)Compared with Sham group,the microvessel density(MVD)in I/R+saline group was increased([169±6]vs.[74±1

关 键 词：尤瑞克林 缺血-再灌注 缓激肽受体B1 缓激肽受体B2 

分 类 号：R73[医药卫生—肿瘤]