Gao Yuan, Cao Xinyu, Zhang Xiaojiao, Wang Yangjun, Huang He, Meng Yonggang, Chang Junbiao
Institute of Pharmacology, Zhengzhou University, Henan, China.
College of Chemistry and Molecular Engineering, Zhengzhou University, Henan, China.
Front Pharmacol. 2020 Feb 21;11:99. doi: 10.3389/fphar.2020.00099. eCollection 2020.
The goal of this study was to elucidate the mechanisms of protection of Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (trade name: Brozopine, BZP) against cerebral ischemia and . 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 NaSO for 2 h, reoxygenation for 24 h) were evaluated. Four and groups were evaluated to characterize targets of BZP: Control group, Model group, BZP group (10 mg/kg)/BZP group (30 μmol/L), C8E4 group (10 mg/kg)/C8E4 group (30 μmol/L). An ELISA kit was used to determine the levels of 15-HETE (a 15-LOX-2 metabolite) and . Rat nuclear factor κB subunit p65 (NF-κB p65), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) were also quantified and . The results showed that BZP improved focal cerebral ischemia-reperfusion injury in rats and PC12 cells treated with NaSO in dose/concentration-dependent manners through inhibition of production of 15-HETE and expression of NF-κB, IL-6, TNF-α, and ICAM-1. In conclusion, BZP exerted protective effects against cerebral ischemia inhibition of 15-LOX-2 activity.
本研究的目的是阐明（±）-5-溴-2-（α-羟基戊基）苯甲酸钠（商品名：Brozopine，BZP）对脑缺血的保护机制。为了探究BZP对局灶性脑缺血再灌注损伤的保护作用，我们评估了不同剂量的BZP对MCAO大鼠（缺血2小时，再灌注24小时）神经行为评分、脑梗死体积、脑肿胀的影响。此外，还评估了不同剂量的BZP对OGD/R诱导的PC12细胞损伤（含30 mmol NaSO的低糖培养基处理2小时，复氧24小时）的影响。评估了四组以表征BZP的作用靶点：对照组、模型组、BZP组（10 mg/kg）/BZP组（30 μmol/L）、C8E4组（10 mg/kg）/C8E4组（30 μmol/L）。使用ELISA试剂盒测定15-HETE（15-LOX-2代谢产物）的水平。还对大鼠核因子κB亚基p65（NF-κB p65）、肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）和细胞间黏附分子-1（ICAM-1）进行了定量分析。结果表明，BZP通过抑制15-HETE的产生以及NF-κB、IL-6、TNF-α和ICAM-1的表达，以剂量/浓度依赖性方式改善了大鼠和经NaSO处理的PC12细胞的局灶性脑缺血再灌注损伤。总之，BZP通过抑制15-LOX-2活性对脑缺血发挥保护作用。
