脑脉通对老龄大鼠脑缺血/再灌注微血管生成及Flk-1表达的影响  

Influences of Naomaitong on angiogenesis and Flk-1 expression in aged rats after cerebral ischemia-reperfusion

作　　者：刘轲[1,2] 李建生[2] 杨歆科[2] 高剑峰[2] 周友龙[2] 赵跃武[3] 刘政国[3] 刘敬霞[2] 

机构地区：[1]河南中医学院第一附属医院,河南450000 [2]河南中医学院老年医学研究所 [3]河南省人民医院病理科

出　　处：《北京中医药大学学报》2011年第1期42-47,共6页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.30371812);河南省杰出青年基金项目(No.0612000700)

摘　　要：目的从胚胎肝激酶-1（Flk-1）因子表达变化揭示脑脉通促进老龄大鼠脑缺血/再灌注血管生成的作用机制。方法将SD雄性老龄大鼠随机分为假手术组、模型组、尼莫地平组、脑脉通组,采用免疫组化和原位杂交等方法测定脑微血管密度（MVD）、血管场面积以及Flk-1的蛋白与mR-NA表达。结果脑脉通组缺血3 h和缺血/再灌注1、3、12 d的MVD,缺血3 h和缺血/再灌注3、6、12 d血管场面积,均较模型组升高（P〈0.05,P〈0.01）;与尼莫地平组比较,脑脉通组缺血/再灌注12 d MVD增加（P〈0.01）,缺血3 h血管场面积增大（P〈0.01）。模型组MVD自缺血3 h持续下降至缺血/再灌注12 d;血管场面积缺血/再灌注1 d达到峰值,然后迅速下降,至12 d降至最低。脑脉通组MVD缺血3 h明显增加,缺血/再灌注1 d达到峰值,然后开始下降,缺血/再灌注6 d降至最低,至12 d又明显增加;血管场面积缺血3 h有明显增加,缺血/再灌注1 d降至最低,3 d时有所升高,至6 d再次降低,随后再次升高,至12 d恢复至缺血/再灌注3 d时水平。脑脉通组各时间点Flk-1表达均较模型组增强（P〈0.05,P〈0.01）;与尼莫地平组比较,脑脉通组缺血/再灌注1、6、12 d Flk-1表达增强（P〈0.05,P〈0.01）,缺血/再灌注3 d Flk-1表达减弱（P〈0.01）。模型组Flk-1表达于缺血3 h开始增强,缺血/再灌注1 d达到峰值,1~12 d表达迅速减弱;脑脉通组Flk-1于缺血3 h有较强表达,缺血/再灌注3 d达到峰值,此后表达稍有减弱,至12 d表达仍处于较高水平。脑脉通组各时间点Flk-1 mRNA表达水平均较模型组增强（P〈0.01）;与尼莫地平组比较,脑脉通组缺血/再灌注6、12 d Flk-1 mRNA表达水平增强（P〈0.01）。模型组Flk-1 mRNA表达于缺血/再灌注1 d最强,1~12 d迅速下降;脑脉通组Flk-1 mRNA缺血3 h即有较高表达,缺血/再灌注1 d达峰值,此后逐渐下降,至12 d表达仍能维持一个较高水平。结论脑脉通可促进老年�Objective To reveal the promoting mechanism of Naomaitong on cerebral angiogenesis after cerebral ischemia/reperfusion（I/R） in aged rats based on the expressions of fetal liver kianse-1（Flk-1）.Methods Male and aged SD rats were randomly divided into the sham-operation group,model group,nimodipine group and Naomaitong group.The microvessel density（MVD） of brain tissue,area of vascular field,and expressions of Flk-1 and Flk-1-mRNA were detected by using immunohistochemistry and hybridization in situ.Results Compared with the model group at the same time point,both MVD [ischemia（I） for 3 h,and I/R for 1 d,3 d and 12 d] and area of vascular field（I for 3 h,and I/R for 3 d,6 d and 12 d） in the Naomaitong group were increased（P0.05,P0.01）.Compared with the nimodipine group,both MVD（I/R for 12 d） and the area of vascular field（I for 3h） in Naomaitong group were increased（P0.01）.In the model group MVD lasted to descend from I for 3 h to I/R for 12 d,the are of vascular field reached peak after I/R for 1 d,then decreased quickly,and reached the lowest level after I/R for 12 d.The area of vascular field（I/R for 1 d） reached peak,then decreased quickly and to the lowest level after 12 days.In the Naomaitong group MVD increased significantly after I for 3 h,reached peak after I/R for 1 d,then started to decrease after,reached the lowest level after I/R for 6 d,and increased significantly after I/R for 12 d,and the area of vascular field increased significantly after I for 3 h,decreased to the lowest level after I/R for 1 d,increased a little after I/R for 3 d,decreased again after I/R for 6 d,and then increased again and recovered to the level of I/R for 3 d after I/R for 12 d.The expressions of Flk-1 in the Naomaitong group at all time points increased compared with the model group（P0.05,P0.01）.Compared with the nimodipine group,expressions of Flk-1 in the Naomaitong group after I/R for 1 d,6 d and 12 d increased（P0.05,P0.01）,while decreased after I/R for 3 d（P0.01）.In the

关 键 词：脑脉通 老龄 脑缺血/再灌注 血管生成 胚胎肝激酶-1 大鼠 

分 类 号：R285.5[医药卫生—中药学]