乐脉颗粒对局灶性脑缺血再灌注大鼠侧支循环形成的影响及机制研究  

Effect of Lemai granule on collateral circulation formation in rats with focal cerebral ischemia-reperfusion and study of its mechanism

作　　者：曹建伟[1] 樊振梅 石素芳 赵丽静[1] 马冠峰[1] 郜风清 CAO Jian-wei;FAN Zhen-mei;SHI Su-fang;ZHAO Li-jing;MA Guan-feng;GAO Feng-qing(Department of Neurology,the Second Affiliated Hospital of Xingtai Medical College,Xingtai 054000,China)

机构地区：[1]邢台医学高等专科学校第二附属医院神经内科,河北邢台054000 [2]冀中能源邢台矿业集团有限责任公司章村分公司医院,河北邢台054000

出　　处：《武警后勤学院学报（医学版）》2019年第5期7-11,21,F0002,共7页Journal of Logistics University of PAP（Medical Sciences）

基　　金：邢台市科技计划支撑项目（2017CZ037）

摘　　要：【目的】探究乐脉颗粒对局灶性脑缺血再灌注大鼠侧支循环形成的影响及其作用机制。【方法】72只大鼠随机分为假手术组、模型组、乐脉颗粒低(0.25 g/kg)、中(0.5 g/kg)、高(1 g/kg)剂量组、尼莫地平组(10 mg/kg),采用大脑中动脉线栓法制备脑缺血再灌注大鼠模型,造模后以不同剂量乐脉颗粒及尼莫地平灌胃治疗,持续7 d,参照Longa分级法对神经功能缺损进行评分,三苯基氯化四氮唑染色观察各组大鼠脑组织梗死面积,免疫组织化学检测CD31阳性细胞表达情况,RT-qPCR检测脑组织中miR-126、血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达水平,Western blotting法检测脑组织中VEGF蛋白的表达水平。【结果】与假手术组相比,模型组大鼠神经功能缺损评分、脑梗死面积、CD31阳性细胞表达、miR-126、VEGF mRNA表达以及VEGF蛋白表达均升高(P<0.05)。与模型组相比,乐脉颗粒各剂量组及尼莫地平组大鼠神经功能缺损评分、脑梗死面积均降低,CD31阳性细胞表达、miR-126、VEGF mRNA表达以及VEGF蛋白表达均升高且乐脉颗粒各组呈剂量依赖性(P<0.05);乐脉颗粒高剂量组与尼莫地平组相比,无明显差异(P>0.05)。【结论】乐脉颗粒可促进局灶性脑缺血再灌注大鼠侧支循环形成,可能是通过上调miR-126/VEGF通路实现。【Objective】To explore the effect of Lemai granule on collateral circulation formation in rats with focal cerebral ischemiareperfusion and its mechanism.【Methods】A total of 72 rats were randomly divided into sham operation group, model group, groups of Lemai granule in low(0.25 g/kg), medium(0.5 g/kg) and high(1 g/kg) doses, and nimodipine group(10 mg/kg). The rat model of cerebral ischemia-reperfusion was established by middle cerebral artery occlusion, then the rats were treated with different doses of Lemai granule and nimodipine by gavage for 7 days. According to Longa grading method, neurological deficits were scored. The infarct size of brain tissue was observed by triphenyltetrazolium chloride(TTC) staining. The expression of CD31 positive cells was detected by immunohistochemistry. The expression of miR-126 and VEGF mRNA in brain tissue was detected by real-time fluorescence quantitative analysis(RT-qPCR). The expression of vascular endothelial growth factor(VEGF) in brain tissue was detected by Western blotting.【Results】Compared with the sham operation group, the neurological deficit score, cerebral infarction area, expression of CD31 positive cells, miR-126, VEGF mRNA and VEGF protein were all increased in the model group(P < 0.05). Compared with the model group, the neurological deficit score and cerebral infarction area of rats in different doses of Lemai granule groups and nimodipine group were decreased, while the expression of CD31 positive cells, miR-126, VEGF mRNA and VEGF protein were increased and there was a dose-dependent manner in Lemai granule groups(P < 0.05). There was no significant difference between high-dose Lemai granule group and nimodipine group(P > 0.05).【Conclusion】Lemai granule can promote collateral circulation formation in rats with focal cerebral ischemia reperfusion, which may be achieved by up-regulating miR-126/VEGF pathway.

关 键 词：乐脉颗粒 脑缺血再灌注 MIR-126 血管内皮生长因子 侧支循环 

分 类 号：R743.3[医药卫生—神经病学与精神病学]