丁苯酞促进心肌梗死大鼠血管再生的作用研究  

Protective effects of dl-3-n-butyphthalide on angiogenesis in myocardial infarction rats

作　　者：田小超[1] 何伟亮[2] 贾妍[1] 武宇洲[1] 金鑫[1] 刘素云[1] TIAN Xiao-chao;HE Wei-liang;JIA Yan;WU Yu-zhou;JIN Xin;LIU Su-yun(Department of Cardiology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China;Department of Neurology,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北医科大学第二医院心内科,河北石家庄050000 [2]河北省人民医院神经内科,河北石家庄050051

出　　处：《河北医科大学学报》2020年第1期12-16,共5页Journal of Hebei Medical University

基　　金：国家自然科学基金青年科学基金(81801312);河北省自然科学基金青年科学基金(H2018206233);河北省医学科学研究重点课题(20180328)

摘　　要：目的探讨丁苯酞(dl-3-n-butyphthalide,NBP)对心肌梗死大鼠血管再生的促进作用及其相关机制。方法取SD大鼠建立心肌梗死模型,分为假手术(Sham,0.9%氯化钠注射液)组、心肌梗死(MI)组、NBP低剂量(NBP-L,20 mg/kg)组和NBP高剂量(NBP-H,40 mg/kg)组,每组6只大鼠。每天给药1次,连续给药2周。通过氯化三苯基四氮唑染色计算心肌梗死面积,超声心动图检测心脏功能,免疫组织化学染色检测心肌梗死边缘区新生血管密度,实时荧光定量PCR检测心肌组织中血管生长因子(vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子(basic fibroblast growth factor,β-FGF)以及Notch 1基因表达情况。结果Sham组大鼠均未见心肌梗死灶,MI组、NBP-L组和NBP-H组大鼠心肌梗死面积百分率大于Sham组,NBP-L组和NBP-H组大鼠心肌梗死面积百分率小于MI组,NBP-H组大鼠心肌梗死面积百分率小于NBP-L组(P<0.05)。MI组、NBP-L组和NBP-H组大鼠LVESP、+dp/dt max、-dp/dt max低于Sham组,LVED高于Sham组,NBP-L组和NBP-H组大鼠LVESP、+dp/dt max、-dp/dt max高于MI组,LVED低于MI组,NBP-H组大鼠LVESP、+dp/dt max、-dp/dt max高于NBP-L组,LVED低于NBP-L组(P<0.05)。NBP-L组和NBP-H组心肌梗死边缘区毛细血管密度高于MI组,NBP-H组心肌梗死边缘区毛细血管密度高于NBP-L组(P<0.05)。MI组大鼠心肌VEGF、β-FGF mRNA水平低于Sham组,NBP-L组和NBP-H组VEGF和β-FGF mRNA水平高于Sham组和MI组,NBP-H组VEGF和β-FGF mRNA水平高于NBP-L组(P<0.05)。MI组大鼠心肌组织中Notch 1基因表达明显低于Sham组,NBP-L组和NBP-H组大鼠心肌中Notch 1基因表达高于Sham组和MI组,NBP-H组大鼠心肌中Notch 1基因表达高于NBP-L组(P<0.05)。结论NBP能够促进心肌梗死后大鼠血管再生,并且可能与激活Notch 1通路有关。Objective To study protective effects of dl-3-n-butyphthalide(NBP)on angiogenesis in rats with myocardial infarction and explore its related mechanism.Methods Myocardial infarction model in SD rats was used.The rats were divided into sham operation group,myocardial infarction(MI)group,the NBP low-dose group(20 mg/kg)and the NBP high-dose group(40 mg/kg).There were 6 rats in each group.The NBP was injected to rats once a day for 2 weeks.2,3,5-Triphenyltetrazolium chloride staining was used to detect myocardial infarction areas.The cardiac functions were evaluated using echocardiography.New blood capillaries density in myocardial infarction fringe area was measured by immunohistochemical analysis.The gene expressions of vascular growth factor(VEGF),basic fibroblast growth factor(β-FGF),and Notch 1 were determined by RT-qPCR.Results No myocardial infarction was found in the Sham group.The percentage of myocardial infarction area in MI group,NBP-L group and NBP-H group was higher than Sham group.However,it was lower in NBP-L group and NBP-H group than that in MI group,and it was lower in NBP-H group than that in NBP-L group(P<0.05).LVESP,+dp/dt Max and-dp/dt Max of rats in the MI,NBP-L and NBP-H groups were lower than those in the Sham group,while LVED was higher than those in the Sham group.LVESP,+dp/dt Max and-dp/dt Max of rats in the NBP-L group and NBP-H group were higher than those in the MI group,while LVED was lower than those in the MI group.LVESP,+dp/dt Max and-dp/dt Max of rats in the NBP-H group were higher than those in the NBP-L group,and LVED in the NBP-H group was lower than those in the NBP-L group(P<0.05).The capillary density in the edge of myocardial infarction in NBP-L group and NBP-H group was higher than that in MI group,and it was higher in NBP-H group than that in NBP-L group(P<0.05).The mRNA level of VEGF andβ-FGF in MI group was lower than that in Sham group,however,in NBP-L group and NBP-H group was higher than that in Sham group and MI group,and the mRNA level of VEGF andβ-FGF in NBP-H

关 键 词：心肌梗死 丁苯酞 血管再生 

分 类 号：R542.22[医药卫生—心血管疾病]