膜粘連蛋白Ⅱ通過保護血腦屏障促進小鼠顱腦創(chuàng)傷后早期神經(jīng)功能的恢復
本文選題:膜粘連蛋白Ⅱ + 創(chuàng)傷性顱腦損傷 ; 參考:《第三軍醫(yī)大學學報》2017年18期
【摘要】:目的評估外源性重組膜粘連蛋白Ⅱ(annexin 2,A2)對創(chuàng)傷性顱腦損傷后血腦屏障以及早期神經(jīng)功能預后的影響,探討A2蛋白作為腦創(chuàng)傷治療靶點的可能性。方法在成年雄性小鼠上建立控制性皮質(zhì)損傷模型(controlled cortical impact,CCI),檢測傷前與傷后不同時間點傷側半球腦組織中內(nèi)源性A2蛋白的表達。隨后,小鼠CCI傷后通過尾靜脈注射重組人源性A2蛋白,并檢測血腦屏障通透性、大腦半球組織含水量、緊密連接蛋白表達量、海馬區(qū)神經(jīng)元數(shù)量、傷灶體積及早期行為學改變。結果從CCI后3 d起,A2蛋白表達明顯增高,并在7 d時達到高峰(P0.05),此后蛋白表達逐漸下降,21 d恢復到基值;傷前內(nèi)皮細胞幾乎不表達A2蛋白,傷后在傷側部分內(nèi)皮細胞表達A2蛋白。在傷后2 h給予重組A2蛋白能顯著降低血腦屏障通透性從而降低腦組織中Evans藍(Evans blue,EB)滲出量(P0.05),增加ZO-1蛋白表達(P0.05),減少傷后CA1和CA3區(qū)神經(jīng)元丟失,CA1區(qū)和CA3區(qū)平均神經(jīng)元存活數(shù)量分別為159.5和131,6,均顯著高于對照組(P0.05),并促進傷后7 d內(nèi)運動功能康復(P0.05)。能夠減少致傷后腦組織含水量,但不具有統(tǒng)計學差異(P0.05),兩組間傷灶體積也無統(tǒng)計學差異(P0.05)。結論在創(chuàng)傷性顱腦損傷早期,給予重組人A2蛋白能提高內(nèi)皮細胞ZO-1合成,保護血腦屏障,減輕神經(jīng)組織繼發(fā)性損傷,促進傷后神經(jīng)功能恢復。
[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.
【作者單位】: 重慶醫(yī)科大學附屬第一醫(yī)院神經(jīng)外科;
【分類號】:R651.15
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