Effects Of Different Doses Of Dl-3n-butylphthalide Stimulating Factors Expression Of HIF-1?,Survivin And Vascular Regeneration In Rats With Cerebral Ischemia-reperfusion Injury

Objective:To observe the effects of different doses of dl-3n-butylphthalide(NBP)stimulating factors expression of HIF-1 ?,Survivin and vascular regeneration in rats with cerebral ischemia-reperfusion injury,and to explore its significance.Methods:A total of 40 male Sprague wrote-Dawley(SD)rats were randomly divided into 5groups:the sham operation group,the model group,the low-dose NBP treatment grop,the medium-dose and the high-dose group.The cerebral ischemia-reperfusion model was established by modified longa suture method.The rats in the NBP group were received intra-abdominal injection of NBP at 20,40,80 mg�Kg-1,respectively,the sham operation group,and the model group were received the same volume of Tween 80.The neurological function was scored with longa in 24 h after reperfusion,the brain pathology morphology were observed by HE stain,the expression of HIF-1?,Survive and CD31 which indicated the expression changes of microvascular ischemic penumbra were detected by immunohistochemistry.Results:The sham operation group did not show any neurologic deficits,the number of microvascular,the grey value of HIF-1? and the grey value of Survivin in ischemicpenumbra were respectively 2.5�1.2,174.6�9.9,163.0�5.8;there were visible neurologic deficits where most cell vacuoles degeneration,the nucleus dissolutionand fracture,microvascular regeneration by HE stain in the model group and the NBP treatment group,the numbers of microvascular were respectively 4.5�1.2,6.3�1.0,8.3�1.4,8.9�1.5,the grey value of HIF-1a were respectively 138.9�5.0,148.4�6.4,160.8�8.1,162.0�5.3,the grey value of Survivin were respectively 153.9�4.9,146.1�2.8,134.1�6.7,131.3�3.6,compared with sham group the difference was statistically significant(P<0.05).Compared with the model group,the neurological scores was significantly decr eased,and microvascular content increased,the expression HIF-1? declines and Survivn has higher expression in the NBP treatment grops.Among the NBP treatm ent grops,the neurological score in the high-dose group was the lowest,the differen ce between the medium-dose and the high-dose group showed no statistical signifi cance(P>0.05).Conclusion:NBP may adjust expression of HIF-1? and Survivin to reduce the nerve cell d egeneration and accelerate vascular regeneration,prompting NBP plays a neuroprote ctive role in the cerebral ischemia-reperfusion injury,and NBP at a dose of 40 m g�Kg-1 may be the best application dose.