右美托咪定对全脑缺氧缺血损伤大鼠海马内星形胶质细胞VEGF表达的影响

摘要

Objective To explore the influences of dexmedetomidine on expressions of vascular endothelial growth factor (VEGF) of hippocampal astrocytes in rats with hypoxic-ischemic brain damage.Methods Totally 24 SD rats,weighting from 250~280 g,were divided into 3 groups (n=8) with a random number table methods:sham-operation group (group S),the routine cardiopulmonary resuscitation group (group C) and dexmedetomidine group (group D).Hypoxic-ischemic brain damage models in rats were established with asphyxia-induced cardiac arrest method in group C and group D,while rats of group S were given tracheal intubation only rather than occlusion asphyxia.Group D was given load dosage of dexmedetomidine (4 μg/kg) via caudal vein injection before occlusion of trachea,while group S and group C were given same volume of normal saline.Neuropathy disability scores (NDS) were determined at 12 h,24 h,48 h and 72 h after recovery of spontaneous circulation in each group of rats.After determination of NDS at 72 h,the rats were sacrificed to sample hippocampus.TUNEL was used to detect the apoptosis of hippocampal neuron.Immunofluorescence double staining was used to determine VEGF expression in hippocampal astrocytes of rats.Results Compared with group S,NDS scores were significantly increased in group C at each time point (P<0.05).There was no difference between group D and group C in NDS at 12 h (P>0.05);however,rats of group D had significantly decreased NDS at 24 h,48 h and 72 h compared with group C (P<0.05).Apoptosis rate of hippocampal neuron and astrocytes VEGF expressions of group C were higher than those of group S (P<0.05).Compared with group C,apoptosis rate of hippocampal neuron was decreased and astrocytes VEGF expression was increased in group D (P<0.05).Conclusion Dexmedetomidine can reduce hypoxic-ischemic brain damage in rats,and reduce the apoptosis rate of hippocampal neurons.The mechanism may be related to the stimulation of VEGF expression in hippocampus astrocytes.%目的 探讨右美托咪定对全脑缺氧缺血损伤大鼠海马内星形胶质细胞中血管内皮细胞生长因子(Vascular endothelial growth factor,VEGF)表达的影响.方法 取SD大鼠24只,体重250~280 g,采用随机数字表法将其分为3组(n=8):假手术组(S组)、常规复苏组(C组)和右美托咪定组(D组).C组和D组采用窒息后心跳骤停法建立大鼠全脑缺氧缺血损伤模型,S组大鼠仅行气管插管不夹闭窒息,D组于气管夹闭前尾静脉注射负荷剂量右美托咪定4 μg/kg,S组和C组分别给予等容量生理盐水.各组大鼠于自主循环恢复后12、24、48及72 h进行神经功能缺失评分(Neuropathy disability score,NDS),于72 h测定NDS后处死大鼠,取海马组织,采用TUNEL法标记检测海马神经元凋亡情况,采用免疫荧光双标法测定各组大鼠海马内星形胶质细胞VEGF的表达情况.结果 与S组比较,C组各时点NDS评分均显著升高(P<0.05);D组大鼠在12 h时NDS评分与C组比较差异无统计学意义(P>0.05),D组大鼠在24、48和72 h三个时点NDS评分显著低于C组(P<0.05).与S组比较,C组大鼠海马内神经元凋亡率和星形胶质细胞VEGF的表达均升高;与C组比较,D组大鼠海马内神经元凋亡率降低,星形胶质细胞VEGF的表达升高(P<0.05).结论 右美托咪定可减轻全脑缺氧缺血损伤大鼠脑损伤,降低海马内神经元的凋亡率,其机制可能与促进海马内星形胶质细胞上VEGF的表达有关.