摘要
目的探究安菲博肽(ANF)对小鼠缺血性脑损伤的保护作用的抗血小板活化机制。方法用改良线栓法制造小鼠大脑中动脉短暂性闭塞(t MCAO)的缺血性脑损伤模型。小鼠随即分为:假手术组、模型组、脑缺血组、ANF(4、2、1μg/kg)组及阳性药替罗非班(TRF,0. 5 mg/kg)组。ANF组及TRF组在小鼠大脑中动脉短暂性闭塞至脑缺血90min后进行再灌注,1 h后给予ANF或TRF,给药方法为尾静脉注射。在小鼠脑缺血再灌注24 h后,分别使用ELISA法测定各组小鼠血清血小板球蛋白(β-TG)和可溶性P-选择素水平;免疫组化检测各组小鼠的脑组织中血管性假血友病因子(v WF)的表达;免疫荧光法检测各组小鼠脑组织v WF和血小板膜糖蛋白(GP) Ib表达。结果 ANF(4、2μg/kg)可显著降低缺血再灌注24 h后t MCAO小鼠血清中可溶性P-选择素和β-TG的浓度,降低t MCAO小鼠缺血脑组织微血管v WF和GPIb的表达丰度。结论 ANF可能通过抑制血小板的活化从而产生对脑缺血小鼠大脑的保护作用,ANF通过降低微血管GPIbα和v WF的表达丰度,抑制可溶性P-选择素和β-TG的过度释放,进而影响血小板黏附、聚集及血栓形成,从而减轻脑缺血再灌注损伤。
Objective To observe the antiplatelet activation mechanisms of anfibatide on ischemic brain injury protection in mice.Methods The focal cerebral ischemia-reperfusion model was built by the suture method for the right middle cerebral artery occlusion in mice.Male Kunming mice were randomly assigned to six groups including sham group,model group,ANF(4,2,1μg/kg)and positive drug tirofiban(TRF,0.5 mg/kg)treatment groups.In ANF and TRF treatment groups,ANF or TRF were administrated by intravenous injection after 90 min cerebral ischemia followed by 1 h reperfusion.24 h after reperfusion,serumβ-TG and soluble P-selection concentration were measured by ELISA,the vWF protein expression was investigated by immunocytochemistry,abundance of GPIbαand vWF were observed by immunofluorescence.Results ANF(4,2μg/kg)significantly decreased the serum concentration of soluble P-selection andβ-TG in tMCAO mice after 24 hour of reperfusion.ANF also reduced the abundance of GPIbαand vWF expression in the vascular walls of the ischemic hemisphere.Conclusion The protective effect of ANF on focal cerebral ischemia in mice may be related to inhibition of platelet activation,reduction abundance of GPIbαand vWF in ischemic cerebral microvascular,inhibition over release of soluble P-selectin andβ-TG in blood,and this affects platelet adhesion and aggregation and thrombus formation,so as to reduce the focal cerebral ischemia-reperfusion injury.
作者
许哲昊
后世翔
陈春燕
秦志强
王坤
章成
周兰兰
Xu Zhehao;Hou Shixiang;Chen Chunyan;QIN Zhiqiang;WANG Kun;ZHANG Cheng;ZHOU Lanlan(Dept of Pharmacology,Anhui Medical University,Hefei 230032)
出处
《安徽医科大学学报》
CAS
北大核心
2018年第12期1838-1842,共5页
Acta Universitatis Medicinalis Anhui
基金
安徽省高校拔尖人才学术资助重点项目(编号:gxbjZD2016035)
