期刊
FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.00099
关键词
brozopine; middle cerebral artery occlusion; 15-HETE; PC12 cells; OGD; R; inflammation
资金
- Scientific and Technical Innovation Team of Zhengzhou University [201310459017]
- National Significant New Drug Creation The Twelfth-Five-Plan New Drug Candidates [2012ZX09103101-011]
- National Natural Science Foundation of China [81330075]
The goal of this study was to elucidate the mechanisms of protection of Sodium (+/-)-5-bromo-2-(alpha-hydroxypentyl) benzoate (trade name: Brozopine, BZP) against cerebral ischemia in vivo and in vitro. To explore the protective effect of BZP on focal cerebral ischemia-reperfusion injury, we evaluated the effects of various doses of BZP on neurobehavioral score, cerebral infarction volume, cerebral swelling in MCAO rats (ischemia for 2 h, reperfusion for 24 h). In addition, the effects of various doses of BZP on OGD/R-induced-PC12 cells injury (hypoglycemic medium containing 30 mmol Na2S2O4 for 2 h, reoxygenation for 24 h) were evaluated. Four in vivo and in vitro groups were evaluated to characterize targets of BZP: Control group, Model group, BZP group (10 mg/kg)/BZP group (30 mu mol/L), C8E4 group (10 mg/kg)/C8E4 group (30 mu mol/L). An ELISA kit was used to determine the levels of 15-HETE (a 15-LOX-2 metabolite) in vivo and in vitro. Rat nuclear factor kappa B subunit p65 (NF-kappa B p65), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) were also quantified in vivo and in vitro. The results showed that BZP improved focal cerebral ischemia-reperfusion injury in rats and PC12 cells treated with Na2S2O4 in dose/concentration-dependent manners through inhibition of production of 15-HETE and expression of NF-kappa B, IL-6, TNF-alpha, and ICAM-1. In conclusion, BZP exerted protective effects against cerebral ischemia via inhibition of 15-LOX-2 activity.
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