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