脑梗死急性期SD大鼠血清血管内皮细胞生长因子变化特点的实验研究

Experimental study on changes of serum VEGF SD in rats with acute cerebral infarction

目的研究血管内皮细胞生长因子(VEGF)表达水平在SD大鼠脑梗死急性期不同时间点的动态变化,为脑梗死的治疗和相关的药物研制提供新的靶点。方法将雌雄各半的36只SD大鼠分为手术组与假手术组各16只、空白组4只。手术组和假手术两组又各分为A、B、C、D 4个小组。每个小组4只大鼠,雌雄各2只。参照改良线栓法闭塞右侧大脑中动脉,制作大鼠局灶性脑梗死模型。麻醉清醒后进行Longa大鼠神经功能缺损评分和行为检查评估,评分1～3分的大鼠纳入实验,0、4分或取脑时发现脑出血的均淘汰,并在后续实验补足每组大鼠的数量。取1/2、2、3、6、12、24、72、168h共8个时间点断尾采血,用ELISA法测定血液中VEGF的浓度;通过重复测量的方差分析统计手术组、假手术组、空白组VEGF因子在不同时间点的变化特点。结果 VEGF因子的表达在脑梗死后1/2 h出现上调,2、3、6、12 h持续少量增高,在24 h达到高峰,随后表达有所下降,在168 h表达又有所增加。结论 VEGF在SD大鼠脑梗死后1/2 h开始变化,24 h达高峰,参与了脑梗死后的应急表达,是低氧应答的关键因子。

Objective To study the changes of vascular endothelial growth factor（VEGF） expression in SD rats with acute cerebral infarction at different time points,to provide new targets for the treatment and drug development of cerebral infarction.Methods Thirty-six SD rats（male vs female： 1 vs 1） were randomly divided into three groups,surgery group（Group A,n = 16）,sham operation group（Group B,n = 16） and control group（n = 4）.Group A and group B were then further divided into four sub-groups.Each sub-group had 2 male and 2 female rats.Cerebral infarction models were produced by blocking of the right middle cerebral artery according to modified suture method.Longa neurological function scores and behavioral evaluation were practiced after regaining consciousness from anesthesia.Rats scored 1~3 were selected into the test.Rats scored 0 and 4,or with cerebral hemorrhage in the brain were eliminated through selection.The missing rats were made up in the subsequent trial in each group.Blood samplings were taken from tails of rats at 1/2 h,2 h,3 h,6 h,12 h,24 h,72 h and 168 h.The VEGF levels in blood were examined by ELISA analysis.Analysis of variance was used to analyze changes of VEGF in surgical group,sham operation group and control group at different time points.Results The expression of VEGF began to increase at 1/2 h after cerebral infarction,and kept increasing marginally at 2 h,3 h,6 h,12 h,and peaked at 24 h.Then it turned to decrease and happened to increase again at the 168 h（7 d） after cerebral infarction.Conclusions VEGF begins to change 1/2 h and reaches peak 24 h after cerebral infarction,is involved in the emergency expression after cerebral infarction,and is the key factor of hypoxia response