Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Biomed Pharmacother. 2018 Jul;103:1720-1726. doi: 10.1016/j.biopha.2018.05.001.
Stroke is a prevalent disorder which is associated with several complications including inflammation. JZL-184 (JZL) inhibits arachidonic acid (AA) production and consequently results in two-arachidonoylglycerol (2-AG) accumulation. Both reduced production of AA metabolic products and increased 2-AG, the agonist of type 1 cannabinoid receptor (CB1), can result in reduced inflammation. In this study, we investigated the mechanisms of JZL in the improvement of stroke complications in mouse permanent cerebral ischemia (PPMCAO) model using AM251, the antagonist of CB1.
PMCAO mice were divided into six groups including intact, controls, vehicle, JZL, AM251 and JZL plus AM251 administrated groups. Brain infarction and edema, brain levels of matrix metalloperoteinase-9 (MMP9), interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) and behavioral functions have been examined in all groups.
The results showed that JZL lowered brain infarction, neurological disorders, TNF-α and MMP9 more effectively than JZL plus AM251. JZL and JZL plus AM251 reduced brain edema and increased brain IL-10. JZL, AM251 and JZL plus AM251 improve behavioral functions.
JZL reduces brain infarction and brain pro-inflammatory molecules in CB1 pathway dependent manner. JZL also reduces brain edema and increased IL-10 in CB1 pathways or decreased AA metabolites. Further, AM251 improves behavioral functions via unknown mechanisms.
中风是一种常见疾病，与多种并发症相关，包括炎症。JZL-184（JZL）抑制花生四烯酸（AA）的产生，进而导致二花生四烯甘油（2-AG）的积累。AA 代谢产物生成减少和 2-AG 增加，2-AG 是大麻素受体 1 型（CB1）的激动剂，两者都能减轻炎症。在这项研究中，我们使用 CB1 的拮抗剂 AM251 研究了 JZL 在改善小鼠永久性大脑缺血（PPMCAO）模型中风并发症中的作用机制。
PMCAO 小鼠分为六组，包括完整组、对照组、载体组、JZL 组、AM251 组和 JZL 加 AM251 组。检查了所有组的脑梗死和水肿、脑基质金属蛋白酶-9（MMP9）、白细胞介素（IL）-10 和肿瘤坏死因子-α（TNF-α）水平和行为功能。
结果表明，与 JZL 加 AM251 相比，JZL 更有效地降低了脑梗死、神经功能障碍、TNF-α 和 MMP9。JZL 和 JZL 加 AM251 降低了脑水肿并增加了脑 IL-10。JZL、AM251 和 JZL 加 AM251 改善了行为功能。
JZL 以 CB1 途径依赖性方式降低脑梗死和脑前炎症分子。JZL 还通过 CB1 途径或减少 AA 代谢物增加脑水肿和增加 IL-10。此外，AM251 通过未知机制改善行为功能。
