The role of pinocembrin in t-PA thrombolysis-induced hemorrhagic transformation
10.16438/j.0513-4870.2018-1062
- VernacularTitle:匹诺塞林在t-PA溶栓所致出血转化中的作用
- Author:
Yan-xia CHEN
1
,
2
;
Ling-lei KONG
3
;
Hai-gang WANG
3
;
Rui-li SHI
1
,
2
;
Guan-hua DU
3
Author Information
1. Department of Physiology, Baotou Medical College, Baotou 014040, China
2. Institute of Neuroscience, Baotou Medical College, Baotou 014040, China
3. Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
hemorrhagic transformation;
tissue plasminogen activator;
pinocembrin;
blood-brain barrier;
ischemic stroke
- From:
Acta Pharmaceutica Sinica
2019;54(3):448-453
- CountryChina
- Language:Chinese
-
Abstract:
Hemorrhagic transformation (HT) is a frequent complication of ischemic stroke, especially after thrombolytic therapy. This event is associated with increased morbidity and mortality. Tissue plasminogen activator (t-PA), the only FDA proved drug for breaking blood clots, is underutilized in ischemic stroke, because of its limited therapeutic window and hemorrhagic complications. Due to the lack of clear understanding of the pathological mechanism, there are no effective drugs to decrease the incidence of HT. Pinocembrin is a natural flavonoid compound and has neuroprotective effects in animal ischemic stroke models. In this study, we investigated the role of pinocembrin in t-PA thrombolysis-induced HT in rat thromboembolic stroke model. t-PA was administrated 6 h after ischemia and pinocembrin (5, 10 and 20 mg·kg-1) was given 5 min before t-PA administration. Infarct volume, neurological score and hemoglobin content were evaluated at 24 h after ischemia. Evans blue leakage was used to detect blood-brain barrier (BBB) permeability. All procedures were approved by the Institutional Animal Care and Use Committee of the Peking Union Medical College. The results showed that treatment with t-PA at 6 h after ischemia aggravated brain injury and increased the risk of HT, with infarct volume and brain water content reached 39% and 83.4%, respectively. Pretreatment with pinocembrin decreased the infarct volume and brain water content to 28.5% and 80.3%, and improved neurological function. In addition, the combined application of pinocembrin with t-PA reduced hemoglobin content and Evans blue content in brain tissue by 50% and 40%, indicating that pinocembrin could protect the BBB permeability and reduce the occurrence of HT. Among these doses, 10 mg·kg-1 is most effective. In conclusion, our results demonstrate that the combination of pinocembrin with t-PA protects against cerebral ischemia, reduces the occurrence of HT induced by t-PA thrombolysis. Thus, pinocembrin may be a potential therapeutic drug for t-PA induced HT.
