当归对慢性脑低灌注大鼠血脑屏障的保护作用

Protective effect of Angelica sinensis on blood-brain barrier in rats with chronic cerebral hypoperfusion

目的:探讨当归(AS)对慢性脑低灌注(CCH)大鼠血脑屏障(BBB)的影响。方法:使用双侧颈总动脉结扎(2VO)建立CCH模型。36只成年雄性SD大鼠随机分为假手术(Sham)组、2VO组以及AS治疗组(2VO+AS1 g/kg),每组12只。治疗14 d后,通过行为学测试观察大鼠学习及记忆功能并使用激光多普勒血流仪检测大鼠海马血流量。伊文思蓝(EB)渗透实验用于评估血脑屏障通透性,并使用Western Blot检测海马紧密连接蛋白claudin-5、ZO-1及基质金属蛋白酶9(MMP-9)的蛋白表达水平。结果:与Sham组相比,2VO大鼠出现明显的认知损害及海马血流量的下降,海马EB渗出量升高且claudin-5、ZO-1蛋白表达水平降低,MMP-9水平升高。与2VO组相比,AS治疗组认知损害明显改善,海马血流量升高。同时,AS组海马EB渗出量降低,海马claudin-5、ZO-1水平升高,MMP-9水平显著降低。结论:AS治疗可以改善CCH造成的血脑屏障破坏及认知损害。

Objective:To investigate the effect of Angelica sinensis(AS)on the blood-brain barrier of chron-ic cerebral hypoperfusion(CCH)rats.Methods:CCH model was established by bilateral common ca-rotid artery ligation(2 VO).Thirty-six adult male SD rats were randomly divided into a Sham opera-tion group,a 2 VO group,and an AS treatment group(2 VO+AS 1 g/kg),with 12 rats in each group.After 14 days of treatment,behavioral tests were performed to observe the learning and memo-ry function of the rats,and the blood flow in hippocampus of the rats was measured using a laser Dop-pler flowmeter.Evans blue(EB)penetration assay was used to assess blood-brain barrier permeabili-ty,and Western Blot was used to detect hippocampal claudin-5,ZO-1,and matrix metalloproteinase9(MMP-9)protein expression levels.Results:Compared with the Sham group,2 VO rats showed sig-nificant cognitive impairment and decreased hippocampal blood flow and increased hippocampal EB ex-udation.The expression levels of claudin-5 and ZO-1 proteins in the hippocampus were reduced,and the levels of MMP-9 were increased.Compared with the 2 VO group,cognitive impairment in the AS treatment group was significantly alleviated,and hippocampal blood flow was increased.Meanwhile,hippocampal EB exudation decreased in the AS group,the levels of claudin-5 and ZO-1 in the hippo-campus increased,and the level of MMP-9 decreased significantly.Conclusion:AS treatment can im-prove blood-brain barrier damage and cognitive impairment caused by CCH.