促红细胞生成素经鼻给药对缺血再灌注大鼠神经功能及脑组织CD31的影响  

Effects of erythropoietin administrated by intranasal on nerve function and CD31 in cerebral ischemia reperfusion rats

作　　者：韩翔宇[1] 宋大庆[1] 朱瑞云[1] 于永梅[2] 张延波[3] 杨明峰[3] 孙保亮[3] Han Xiangyu1, Song Daqing1, Zhu Ruiyun1, Yu Yongmei2, Zhang Yanbo3, Yang Mingfeng3 , Sun Baoliang3(1. Emergency Department of lnternal Medicine,Jining No. 1 People＇s Hospital,Jining 272000, China ; 2.Department of Radiology,Jining No. 1 People＇s Hospital,Jining 272000, China ;3.Department of Neurology,the Affiliated Hospital of Taishan Medical University;Key Lab of Cerebral Microcirculation In Universities of Shandong , Taian 271000, China)

机构地区：[1]山东省济宁市第一人民医院急诊内科,济宁272000 [2]山东省济宁市第一人民医院放射科,济宁272000 [3]泰山医学院附属医院神经内科,山东省高校脑微循环重点实验室,泰安271000

出　　处：《中华行为医学与脑科学杂志》2018年第9期783-787,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：山东省医药卫生科技发展计划项目（2013WS0055,2014WS0273,2016WS0146）;济宁市科技发展计划项目（2014jnnk24）

摘　　要：目的探讨经鼻腔给予促红细胞生成素（erythropoietin，EPO）对急性脑缺血再灌注大鼠的神经功能及脑组织CD31表达的影响。方法100只SD大鼠随机分为模型对照组、假手术组、腹腔给药组（IPEPO组）、鼻腔生理盐水（INNS）组和鼻腔给药组（INEPO）组，每组20只。采用线栓法制作大脑中动脉闭塞模型（MCAO），NSS法对大鼠进行神经行为学评分。酶联免疫吸附技术检测EPO在大鼠外周血、脑脊液及各脑区的表达，荧光免疫法检测血管内皮生长因子在脑内的表达并计数脑内新生血管密度。结果术后15d，INEPO组大鼠的NSS评分[（3．80±1．61）分]较IPEPO组[（11．53±2．11）分]有明显降低，差异有统计学意义（P〈0．01）。IPEPO组大鼠的血液、脑脊液和各脑区的EPO含量较INNS组均明显升高，差异有统计学意义（均P〈0．01）。INEPO组大鼠脑脊液与与各脑区EPO含量较IPEPO组明显升高，差异有统计学意义（均P〈0．01），其中嗅球浓度变化最明显[INEPO组：（1456．90±128．22）pg／ml，IPEPO组：（426．11±36．68）pg／ml，P〈0．01]。术后72h，与假手术组（5．14±1．28）相比，模型对照组（18．21±3．45）、INNS组（18．54±2．58）、IPEPO组（27．01±2．13）和INEPO组（35．52±2．79）大鼠缺血半暗带CD31表达均升高，差异有统计学意义（均P〈0．05）。IPEPO组和INEPO组的CD31表达均较INNS组明显增加，差异有统计学意义（P〈0．05），IN-EPO组相对于IPEPO组，CD31的表达也明显增加，差异有统计学意义（P〈0．05）。结论鼻腔给予EPO能有效改善缺血再灌注大鼠的神经功能，并能上调大鼠脑组织CD31的表达，其效果优于腹腔给药途径。Objective To explore the protective effect of erythropoietin（EPO） administrated by intranasal on cerebral ischemia reperfusion in rats with acute cerebral infarction reperfusion. Methods Total of 100 SD rats were divided into model control group, sham operation group, intraperitoneal administration group （IPEPO group）, nasal saline group （INNS group） group, and nasal drug delivery group （INEPO group） with 20 in each group. The middle cerebral artery occlusion model of rat was established by thread embolism method and the NSS method was used to evaluate the neural behavior of rats. The expression of EPO in peripheral blood, cerebrospinal fluid and brain regions of rats were detected by Elisa. The vascular endothelial growth factor（VEGF） in brain was detected by immunofluoreseence and then the density of newborn blood vessels in the brain was measured. Results Fifteen days after the operation, the NSS score of INEPO group（ 3.80± 1.61 ） was significantly lower than that of IPEPO group （ 11.53±2. 11 ）, and the difference was statistically significant（P〈0.01 ）. And the levels of EPO in blood, eerebrospinal fluid and different brain regions of rats in INEPO group were higher than that of INNS group（ all P〈0.01 ）. Compared with IPEPO group, the level of EPO cerebrospinal fluid and different brain regions of rats in INEPO group increased obviously, the difference was statistically significant （all P〈0. 01 ）, and the EPO concentration of the olfactory bulb was the most obvious （ INEPO group ： （ 1 456.90± 128.22 ） pg/ml, IPEPO group ： （ 426. 11 ± 36.68 ） pg/ml,P〈0.01 ）. Seventy-two hours after operation, the expression of CD31 in ischemic penumbra of rats of model control group （18.21±3.45） ,INNS group（ 18.54±2.58）, IPEPO group（27.01±2. 13） and INEPO group（35.52±2.79） was increased compared with sham operation group （ 5.14± 1.28 ） , and the difference was statistically significant （all P〈0.05）. The expression of CD31 in IPEPO

关 键 词：鼻腔给药 促红细胞生成素 缺血再灌注 血管新生 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]