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Simvastatin pretreatment ameliorates t-PA–induced hemorrhage transformation and MMP-9/TIMP-1 imbalance in thromboembolic cerebral ischemic rats

Simvastatin pretreatment ameliorates t-PA–induced hemorrhage transformation and MMP-9/TIMP-1 imbalance in thromboembolic cerebral ischemic rats

Authors :
Yin,Bo
Li,Dan-Dong
Xu,Shang-Yu
Huang,Huan
Lin,Jian
Sheng,Han-Song
Fang,Jun-Hao
Song,Jin-Ning
Zhang,Ming
Yin,Bo
Li,Dan-Dong
Xu,Shang-Yu
Huang,Huan
Lin,Jian
Sheng,Han-Song
Fang,Jun-Hao
Song,Jin-Ning
Zhang,Ming
Publication Year :
2019

Abstract

Bo Yin,*,1 Dan-Dong Li,*,2,3 Shang-Yu Xu,3 Huan Huang,4 Jian Lin,3 Han-Song Sheng,3 Jun-Hao Fang,3 Jin-Ning Song,2 Ming Zhang11Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workBackground: The use of thrombolysis with tissue-plasminogen activator (t-PA) in patients with acute ischemic stroke (AIS) is limited by increased levels of matrix metalloproteinase-9 (MMP-9) and by the increased risk of hemorrhagic transformation (HT). In this study, we investigated the effects of simvastatin pretreatment on t-PA-induced MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and HT aggravation in a rat AIS model.Methods: The rat AIS model was established by autologous blood emboli. Two weeks before surgery, rats were pretreated with simvastatin (60 mg/kg/d), and three hours after surgery, t-PA (10 mg/kg) was administered. MMP-9 and TIMP-1 levels in the infarcted zone and plasma were evaluated by Western blot analysis and ELISA; the level of HT was quantified by determining the hemoglobin content. RhoA activation was determined to clarify the potential effect.Results: The results suggested that pretreatment with simvastatin suppressed the increase in t-PA-induced MMP-9 levels and neutralized the elevated MMP-9/TIMP-1 ratio, but had no effect on TIMP-1 levels. Thrombo

Details

Database :
OAIster
Notes :
text/html, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1113861808
Document Type :
Electronic Resource