Kudiezi Injection^® Alleviates Blood–Brain Barrier Disruption After Ischemia‐Reperfusion in Rats

Abstract

OBJECTIVE: This study was designed to examine the effect of KDZ, on the BBB disruption in rat underwent MCAO and reperfusion. METHODS: Male Sprague-Dawley rats (260-280 g) were subjected to 60 minutes MCAO followed by reperfusion. KDZ (4 mL/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. RESULTS: I/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. CONCLUSIONS: KDZ 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 its main ingredients to bind to Src and inhibit its phosphorylation.