Kudiezi Injection® Alleviates Blood-Brain Barrier Disruption After Ischemia-Reperfusion in Rats
Kudiezi Injection® Alleviates Blood-Brain Barrier Disruption After Ischemia-Reperfusion in Rats
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DOI：
10.1111/micc.12288
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发表时间：
2016-08-01
期刊：
影响因子：
2.4
通讯作者：
Han, Jing-Yan
中科院分区：
文献类型：
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作者：
Chen, Fu-Qin;Li, Quan;Han, Jing-Yan
目的本研究旨在探讨苦碟子对大鼠MCAO和再灌注血脑屏障破坏的影响。方法对雄性Sprague-Dawley大鼠(260-280g)进行60分钟MCAO再灌注。缺血前给予KDZ（4mL/kg）。评估伊文思蓝外渗、白蛋白渗漏、脑含水量、TJ蛋白、caveolin-1、p-caveolin-1、Src和p-Src。评估神经系统评分、脑梗塞和CBF。检测了KDZ与Src的结合亲和力。结果I/R引起一系列损伤，包括伊文思蓝外渗、白蛋白渗漏、脑含水量增加、CBF降低、脑梗塞和神经功能缺损，所有这些都被KDZ减轻。同时，KDZ抑制I/R后TJ蛋白的下调、caveolin-1的表达、caveolin-1和Src的磷酸化。此外，SPR显示KDZ与Src具有高亲和力结合。结论KDZ通过防止TJ蛋白降解、caveolin-1表达以及抑制p-caveolin-1和p-Src来保护BBB免受破坏并改善I/R后的脑结局，这很可能归因于其主要成分与Src结合并抑制其磷酸化的能力。
ObjectiveThis study was designed to examine the effect of KDZ, on the BBB disruption in rat underwent MCAO and reperfusion.MethodsMale Sprague-Dawley rats (260-280g) were subjected to 60minutes MCAO followed by reperfusion. KDZ (4mL/kg) was administrated before ischemia. The Evans blue extravasation, albumin leakage, brain water content, TJ proteins, caveolin-1, p-caveolin-1, Src, and p-Src were evaluated. Neurological scores, cerebral infarction, and CBF were assessed. The binding affinity of KDZ to Src was examined.ResultsI/R evoked a range of insults including Evans blue extravasation, albumin leakage, brain water content increase, CBF decrease, cerebral infarction, and neurological deficits, all of which were attenuated by KDZ. Meanwhile, KDZ inhibited TJ proteins down-expression, expression of caveolin-1, phosphorylation of caveolin-1 and Src after I/R. In addition, SPR revealed binding of KDZ to Src with high affinity.ConclusionsKDZ protects BBB from disruption and improves cerebral outcomes following I/R via preventing the degradation of TJ proteins, caveolin-1 expression, and inhibiting p-caveolin-1 and p-Src, which were most likely attributable to the ability of itsmain ingredients to bind to Src and inhibit its phosphorylation.