实用医学杂志 ›› 2022, Vol. 38 ›› Issue (8): 946-951.doi: 10.3969/j.issn.1006⁃5725.2022.08.007

• 基础研究 • 上一篇    下一篇

生存素抑制剂YM155对脑梗死大鼠微血管密度及血管新生相关基因表达的影响

黄建敏 云艳芳 杨桂新 陈海燕 蒋勇明 黄东旭 刘洁 莫晓榕 李雪斌   

  1. 右江民族医学院附属医院神经内科(广西百色 533000)

  • 出版日期:2022-04-25 发布日期:2022-04-25
  • 通讯作者: 国家自然科学基金项目(编号:81860226)
  • 基金资助:


Effects of survivin inhibitor YM155 on microvessel density and angiogenesis⁃related gene expression in rats with cerebral infarction

HUANG Jianmin,YUN Yanfang,YANG Guixin,CHEN Haiyan,JIANG Yongming, HUANG Dongxu,LIU Jie,MO Xiaorong,LI Xuebin.   

  1. Department of Neurology,Youjiang Medical College For Nationalities,Baise 533000,China 

  • Online:2022-04-25 Published:2022-04-25

摘要:

目的 探讨生存素抑制剂YM155对脑梗死大鼠微血管密度及新生血管相关基因表达的影响。 方法 将120只SD雄性大鼠随机分4组(n = 30):假手术组(Sham 组)、模型组(Model 组)、YM155组(YM组)、 生理盐水对照组(NS组),采用大脑中动脉阻断法构建脑缺血模型,造模成功后第1天,YM组大鼠按6.5 mg/kg 剂量的YM155在腹部皮下注射,NS组大鼠按YM组方法应用等量生理盐水处理。应用免疫组化法检测各组 大鼠脑组织微血管密度(microvessel density,MVD)的变化,采用RT⁃PCR和免疫印迹法检测各组大鼠脑组织中 Survivin、VEGF、ES、TSP⁃1 mRNA及其蛋白表达的变化。结果 与Sham 组比较,Model组和NS组MVD显著增 高,与Model组比较,YM组MVD显著降低,差异有统计学意义(P < 0.01)。与Sham组比较,Model组和NS Survivin、VEGF mRNA及蛋白表达显著增加,而ES、TSP⁃1 mRNA及蛋白表达显著降低,差异均有统计学意义 P < 0.01);与Model组比较,YM组Survivin、VEGF mRNA及蛋白表达显著降低,而ES、TSP⁃1 mRNA及蛋白表 达显著增加,差异也均有统计学意义(P < 0.01)。结论 YM155可降低MVD,与Survivin、VEGF 表达下调和 ES、TSP⁃1表达上调有关,提示这些因子相互作用、相互影响可能是脑侧支循环建立和形成的重要机制之一。

关键词:

YM155, 微血管密度, 生存素, 血管内皮生长因子, 内皮抑素, 血小板反应蛋白?1, 脑梗死, 大鼠

Abstract:

Objective To investigate the effects of survivin inhibitor YM155 on the expression of angio⁃ genesis ⁃ related genes and microvessel density in cerebral infarction rats. Methods A total of 120 SD male rats were randomly divided into a sham group,a model group,a survivin inhibitor YM155 group(YM group),and a normal saline group(NS group),with 30 in each group. A cerebral ischemia model was established by middle cere⁃ bral artery occlusion. From day one after the model establishment,the rats in YM group received abdominal injec⁃ tion subcutaneously at a dose of YM155 of 6.5 mg/kg,while those in NS group received the same amount of normal saline. Immunohistochemistry was applied to detect changes in microvessel density(MVD)in the brain tissues of rats in each group,so were RT⁃PCR and Western blotting to detect expressions of survivin,VEGF,ES,and TSP⁃1 mRNA and protein. Results As compared with sham group,MVD in model group and NS group was significantly elevated;while compared with model group,MVD in YM group decreased significantly,and the difference was statistically significant(P < 0.01). As compared with sham group,the expressions of survivin,VEGF mRNA and protein in model group and NS group increased significantly,while the expressions of ES,tsp⁃1 mRNA and protein decreased significantly,and the difference was statistically significant(P < 0.01). As compared with model group the expressions of survivin,VEGF mRNA and protein in YM group decreased significantly,while the expressions of ES,TSP⁃1 mRNA and protein increased significantly,and the difference was statistically significant(P < 0.01). Conclusions Ym155 can reduce MVD,which is related to the down⁃regulation of survivin and VEGF expressions and the up⁃regulation of ES and TSP⁃1 expressions,suggesting that the interaction of these factors may be one of the important mechanisms for the formation and establishment of cerebral collateral circulation.

Key words: YM155,  , microvessel density,  , survivin,  , vascular endothelial growth factor,  , endostatin,  , thrombospondin?1,  , cerebral infarction,  , rats