刺槐素对小鼠脑缺血再灌注损伤后血脑屏障的影响

The effects of Acacetin on blood-brain barrier after cerebral ischemia-reperfusion injury in mice

目的探讨刺槐素对小鼠脑缺血再灌注损伤后血脑屏障紧密连接主要结构蛋白ZO-1,Occludin和Claudin-5表达水平的影响。方法将18只雄性C57BL/6小鼠采用随机数字法分为假手术组、缺血再灌注组和刺槐素治疗组,每组各6只;刺槐素治疗组再灌注时腹腔注射刺槐素(Acacetin)(25 mg/kg);采用改良线栓法制作大脑中动脉闭塞模型,再灌注24 h后免疫组化测定Occludin,Claudin-5及ZO-1染色阳性细胞数。结果免疫组化染色显示,与假手术组比较,缺血再灌注组无论是皮层还海马,紧密连接蛋白Occludin,Claudin-5及ZO-1染色阳性细胞数显著减少(P<0.01);与缺血再灌注组比较,刺槐素治疗组皮层和海马紧密连接蛋白Occludin,Claudin-5及ZO-1染色阳性细胞数显著增加(P<0.01)。结论刺槐素可能通过增加Occludin,Claudin-5及ZO-1蛋白表达来降低血脑屏障的通透性,从而在脑缺血再灌注损伤中发挥神经保护作用。

Objective To investigate the effects of Acacetin on ZO-1,Occludin and Claudin-5 expressive levels after cerebral ischemia-reperfusion injury in mice.Methods 18 male C57 BL/6 mice were randomly divided into sham operation group,ischemia-reperfusion group and Acacetin treatment group by random number method.Acacetin(25 mg/kg)was intraperitoneally injected during reperfusion in the Acacetin treatment group.The Occludin,Claudin-5 and ZO-1 expression levels was determined by immunohistochemistry after 24 h of reperfusion.The occlusion model of middle cerebral artery was made with modified thread occlusion.Results Immunohistochemistry showed that the Occludin,Claudin-5 and ZO-1 expression levels of tight junction proteins in both cortical and hippocampal areas were significantly decreased in the ischemia-reperfusion group compared with the sham operation group(P<0.01).Compared with the ischemia-reperfusion group,the Occludin,Claudin-5 and ZO-1 expression levels in the cortex and hippocampus of the Acacetin treatment group were significantly increased(P<0.01).Conclusion Acacetin could reduce the permeability of the blood-brain barrier by increasing the Occludin,Claudin-5 and ZO-1 expression levels,and thus play a neuroprotective role in cerebral ischemia-reperfusion injury.