title: [Effect and mechanism of huatuo zaizao extractum on focal cerebral ischemia/reperfusion-induced blood-brain barrier injury in rats].
abstract: 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.
  
  
  METHODS
  Sixty 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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  Cell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.
authors.affiliation: Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Zheng
authors.forename: Ming-Jiang
authors.initials: MJ
authors.lastname: Yao
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Liu
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Sheng-Bo
authors.initials: SB
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Jing-Xi
authors.initials: JX
authors.lastname: Si
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000293:injuries*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004365:Drugs, Chinese Herbal; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9