title: Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats.
abstract: Tissue-type plasminogen activator (t-PA) and matrix metalloproteinase-9 (MMP-9) have been reported to play important roles in increased permeability of blood-brain barrier (BBB) under many pathological circumstances. We have showed that Ulinastatin, a broad-spectrum serine protease inhibitor, could alleviate inflammation in the hippocampus of aged rats following partial hepatectomy. In this study, we investigate the expression and potential roles of t-PA and MMP-9 in the protective effect of Ulinastatin. We found that partial hepatectomy increased Evans blue leakage in hippocampus at day 1 and 3 postoperatively. Furthermore, surgery decreased the protein levels of claudin-5, ZO-1, and NF-kB p65 while upregulating the mRNA and protein levels of t-PA and MMP-9 in brain capillaries. All these effects caused by surgery were partially reversed by administering Ulinastatin. Our study sheds light on the roles of t-PA and MMP-9 of BBB in post-surgical neuroinflammation and postoperative cognitive dysfunction. Besides, it could also help to understand the mechanism of Ulinastatin alleviating neuroinflammation.
authors.affiliation: a Department of Anesthesiology , General Hospital of Beijing Military Command , Beijing , China and.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: b Department of Neurosurgery , Air Force General Hospital of the Chinese PLA , Beijing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Department of Anesthesiology , General Hospital of Beijing Military Command , Beijing , China and.
authors.forename: Yong-zhe
authors.initials: YZ
authors.lastname: Liu
authors.affiliation: a Department of Anesthesiology , General Hospital of Beijing Military Command , Beijing , China and.
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Yin
authors.affiliation: a Department of Anesthesiology , General Hospital of Beijing Military Command , Beijing , China and.
authors.forename: Ya-qun
authors.initials: YQ
authors.lastname: Ma
authors.affiliation: a Department of Anesthesiology , General Hospital of Beijing Military Command , Beijing , China and.
authors.forename: Sheng-suo
authors.initials: SS
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006498:Hepatectomy / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062507:Claudin-5; D006023:Glycoproteins; D016328:NF-kappa B; D014361:Trypsin Inhibitors; D062826:Zonula Occludens-1 Protein; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9; C028665:urinastatin
keywords: blood–brain barrier; neuroinflammation; t-PA, MMP-9; ulinastatin