Effect and mechanism of huatuo zaizao extractum on focal cerebral ischemia/reperfusion-induced blood-brain barrier injury in rats.
- Author:
Yong-Qiu ZHENG
1
;
Ming-Jiang YAO
;
Jian-Xun LIU
;
Wen-Ting SONG
;
Lei LI
;
Sheng-Bo LIU
;
Yan HU
;
Jing-Xi SI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Behavior, Animal; drug effects; physiology; Blood-Brain Barrier; drug effects; injuries; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; pharmacology; G-Protein-Coupled Receptor Kinase 2; metabolism; Gene Expression Regulation, Enzymologic; drug effects; Infarction, Middle Cerebral Artery; complications; Male; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Microvessels; drug effects; Rats; Rats, Sprague-Dawley; Reperfusion Injury; complications; metabolism; physiopathology
- From: China Journal of Chinese Materia Medica 2013;38(4):585-590
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSixty healthy male adult Sprague-Dawley rats was randomly divided into the sham operation group, the MCAO model group, the Tanakan (20 mg x kg(-1)) group, and high, middle and low-dose HTZZ groups (5, 2.5, 1.25 g x 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.
RESULTAfter 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 edemaand blood-brain barrier ultrastructure injury induced by I/R, reduce expression of functional (membrane coupling) GRK2, and inhibit expressions of MMP-2 and MMP-9.
CONCLUSIONCell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.