[Effect and mechanism of huatuo zaizao extractum on focal cerebral ischemia/reperfusion-induced blood-brain barrier injury in rats].

Objective: To observe the effect and mechanism of Huatuo Zaizao extractum(HTZZ) on focal ischemia/reperfusion(I/R) blood-brain barrier injury induced by middle cerebral artery occlusion.Method: Sixty healthy male adult Sprague-Dawley rats was randomly divided into the sham operation group,the MCAO model group,the Tanakan(20 mg·kg-1) group,and high,middle and low-dose HTZZ groups(5,2.5,1.25 g·kg-1),with 10 in each group and single-dose duodenal administration.Middle cerebral artery occlusion was adopted to establish the rat focal I/R model.After ischemia for 90 min and reperfusion for 24 h,the pathological injury at the ischemia side was observed by HE staining.The blood-brain barrier structure was observed under transmission electron microscope.Expressions of G protein-coupled receptor kinases 2(GRK2),matrix metalloproteinases 2(MMP-2) and MMP-9 were detected by western blotting technique.Result: After 90 min MCAO/24 h reperfusion,penumbra cerebral cortical micro-vessels showed edema,mitochondrial injury,vacuolation,membrane injury and reduction.Along with the changes,sub-cells of G protein-coupled receptor kinase 2(GRK2) in cortical penumbra brain tissues transferred from cytoplasm to membrane,with increase in expressions of MMP-2 and MMP-9.HTZZ could effectively recover cerebral micro-vascular endothelial edema and blood-brain barrier ultra-structure injury induced by I/R,reduce expression of functional(membrane coupling) GRK2,and inhibit expressions of MMP-2 and MMP-9.Conclusion: Cell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.