膜粘连蛋白Ⅱ通过保护血脑屏障促进小鼠颅脑创伤后早期神经功能的恢复

发布时间：2018-04-18 06:26

本文选题：膜粘连蛋白Ⅱ + 创伤性颅脑损伤　；参考：《第三军医大学学报》2017年18期

【摘要】：目的评估外源性重组膜粘连蛋白Ⅱ(annexin 2,A2)对创伤性颅脑损伤后血脑屏障以及早期神经功能预后的影响,探讨A2蛋白作为脑创伤治疗靶点的可能性。方法在成年雄性小鼠上建立控制性皮质损伤模型(controlled cortical impact,CCI),检测伤前与伤后不同时间点伤侧半球脑组织中内源性A2蛋白的表达。随后,小鼠CCI伤后通过尾静脉注射重组人源性A2蛋白,并检测血脑屏障通透性、大脑半球组织含水量、紧密连接蛋白表达量、海马区神经元数量、伤灶体积及早期行为学改变。结果从CCI后3 d起,A2蛋白表达明显增高,并在7 d时达到高峰(P0.05),此后蛋白表达逐渐下降,21 d恢复到基值;伤前内皮细胞几乎不表达A2蛋白,伤后在伤侧部分内皮细胞表达A2蛋白。在伤后2 h给予重组A2蛋白能显著降低血脑屏障通透性从而降低脑组织中Evans蓝(Evans blue,EB)渗出量(P0.05),增加ZO-1蛋白表达(P0.05),减少伤后CA1和CA3区神经元丢失,CA1区和CA3区平均神经元存活数量分别为159.5和131,6,均显著高于对照组(P0.05),并促进伤后7 d内运动功能康复(P0.05)。能够减少致伤后脑组织含水量,但不具有统计学差异(P0.05),两组间伤灶体积也无统计学差异(P0.05)。结论在创伤性颅脑损伤早期,给予重组人A2蛋白能提高内皮细胞ZO-1合成,保护血脑屏障,减轻神经组织继发性损伤,促进伤后神经功能恢复。
[Abstract]:Objective to evaluate the effects of exogenous recombinant annexin 2 (annexin 2 A2) on blood-brain barrier (BBB) and early neurological function after traumatic brain injury (TBI), and to explore the possibility of using A2 protein as a target for the treatment of traumatic brain injury (TBI).Methods the controlled cortical injury model was established in adult male mice, and the expression of endogenous A2 protein was detected at different time points before and after injury.After CCI injury, recombinant human A2 protein was injected via tail vein, and the permeability of blood-brain barrier, water content of cerebral hemispheres, expression of tight junction protein, number of neurons in hippocampal area, volume of injury focus and early behavioral changes were detected.Results from the 3rd day after CCI, the expression of A _ 2 protein increased significantly, and reached the peak at 7 days, then gradually decreased to the basic value at 21 days after injury, and almost no A2 protein was expressed in endothelial cells before injury.A2 protein was expressed in the injured endothelial cells after injury.2 h after injury, recombinant A2 protein could significantly reduce the permeability of blood-brain barrier and decrease the efflux of Evans blue Evans bluegrass (EBEBB) in brain tissue, increase the expression of ZO-1 protein, and reduce the loss of neurons in CA1 and CA3 areas of CA1 and CA3 after injury.The numbers of survival were 159.5 and 131 ~ 6, respectively, which were significantly higher than those of the control group (P 0.05), and promoted the rehabilitation of motor function within 7 days after injury (P 0.05).It can reduce the water content of brain tissue after injury, but there is no statistical difference between the two groups, and there is no significant difference in the volume of injured foci between the two groups.Conclusion in the early stage of traumatic brain injury, recombinant human A2 protein can improve the ZO-1 synthesis of endothelial cells, protect the blood-brain barrier, alleviate the secondary injury of nerve tissue and promote the recovery of nerve function after injury.
【作者单位】：重庆医科大学附属第一医院神经外科;
【分类号】：R651.15

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