基于血管新生途径探讨银杏蜜环口服溶液对光化学诱导血栓形成致小鼠脑梗死模型皮质损伤的影响  

Effects of Yinxing Mihuan Oral Solution on Cerebral Infarction Model Cortical Injury Induced by Photochemical Thrombosis in Mice Based on Angiogenesis Pathway

作　　者：姚明江[1,2] 张业昊 王光蕊 任钧国[1,2] 王益民 王勇[3] 赫少清 刘建勋 YAO Mingjiang;ZHANG Yehao;WANG Guangrui;REN Junguo;WANG Yimin;WANG Yong;HE Shaoqing;LIU Jianxun(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Beijing Key Laboratory of Pharmacology of Chinese Materia Medica,Beijing 100091,China;Xi'an Buchang Traditional Chinese Cardio-Cerebrovascular Disease Hospital,Xi’an 710082,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]中药药理北京市重点实验室,北京100091 [3]西安步长中医心脑病医院,西安710082

出　　处：《中国中医基础医学杂志》2023年第9期1463-1467,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：中国中医科学院科技创新工程“脑病学”学科重大攻关项目(C12021A01305);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202007)。

摘　　要：目的 观察银杏蜜环口服溶液(Yinxing Mihuan oral solution,YM)对光化学诱导血栓形成致小鼠脑梗死(photothrombotic stroke,PTs)模型大脑皮质缺血性损伤的影响,同时探讨其在缺血后血管新生方面的作用机制。方法 SPF级雄性C57BL/6J小鼠随机分为假手术组,模型组,金纳多组(12.5 mg/kg),YM低、高剂量组(412 mg/kg,824 mg/kg),每组10只。采用光化学诱导血栓形成法建立小鼠脑梗死模型,术后连续灌胃给药14 d。观察各组动物体质量、神经功能缺损评分变化;激光散斑成像观察各组动物脑血流灌注量;免疫组化法检测皮质缺血灶周围区脑组织CD31、血管性血友病因子(von Willebrand factor,v WF)蛋白表达;实时荧光定量聚合酶链式反应(real time quantitative polymerase chain reaction,RT-qPCR)法检测小鼠缺血灶周围区脑组织血管内皮生长因子(vascular endothelial growth factor,VEGF)、缺氧诱导因子(hypoxia inducible factor,HIF)-1α及血管生长素(angiogenin,ANG)m RNA表达。结果 PTs模型成功建立。与模型组比较,YM高剂量组小鼠神经功能缺损评分明显下降(P<0.05),脑血流变化率明显减少(灌注量明显升高,P<0.05),VEGF、HIF-1α及ANG m RNA表达明显上调(P<0.05);低剂量组CD31蛋白表达、高剂量组v WF蛋白表达明显上调(P<0.05)。结论 YM可改善PTs模型小鼠神经功能缺损,其作用机制可能与促进缺血后的微血管新生,从而增加皮质缺血区域脑血流灌注相关。Objective To investigate Yinxing Mihuan oral solution(YM)on cortical infarction after photothrombotic stroke(PTs)in mice,and its possible mechanism on angiogenesis after cerebral ischemia.Methods Male SPF C57BL/6J mice were randomly divided into the sham group,the model group,the ginaton group(12.5 mg/kg),and the YM low dose(412 mg/kg)and high dose(824 mg/kg)group.Focal cerebral ischemia model was induced by photochemically induced thrombotic method,and the drugs were given by intragastric administration for 14 consecutive days.Then the body weight and neurological deficit score were evaluated,the cerebral blood perfusion was detected by laser speckle contrast imaging(LSI),the protein expression of CD31 and von willebrand factor(vWF)in the infarct border zone was evaluated by immumohistochemical staining,and the mRNA expression of vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1α(HIF-1α)and angiogenin(ANG)in the IBZ was detected by real time quantitative polymerase chain reaction(RT-qPCR).Results The PTs model was successfully established.Compared to the model group,the neurological deficit score was improved(P<0.05),the rate of change in cerebral blood flow was decreased(local cerebral perfusion was increased,P<0.05),and the mRNA expression of VEGF,HIF-1αand ANG were up-regulated(P<0.05)in the YM high dose group.The protein expression of CD31 and vWF were up-regulated respectively in the YM Low and YM high dose group(P<0.05).Conclusion YM could attenuates neurological deficits in photothrombotic stroke mice,and the possible mechanism may be related to angiogenesis induction so as to increase the local cerebral perfusion in the infarct border zone.

关 键 词：银杏蜜环口服溶液 光化学诱导脑梗死 血管新生 脑血流量 

分 类 号：R285.5[医药卫生—中药学]