Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, District of Yuzhong, Chongqing, 400016, China.
Neurochem Res. 2018 Jun;43(6):1283-1296. doi: 10.1007/s11064-018-2545-4. Epub 2018 May 25.
All-trans retinoic acid (ATRA) influences the outcomes of cerebral ischemic reperfusion (CIR) injury, but the mechanism remains unclear. The present study aimed to investigate the effects of ATRA on loss of the blood brain barrier (BBB) following CIR and to explore the possible mechanisms. Transient middle cerebral artery occlusion was performed on male SD rats to construct an in vivo CIR model. Neurological deficits, BBB permeability, brain edema, MRI and JNK/P38 MAPK proteins were detected at 24 h following CIR. We demonstrated that ATRA pretreatment could alleviate CIR-induced neurological deficits, increase of BBB permeability, infarct volume, degradation of tight junction proteins, inhibit MMP-9 protein expression and activity. ATRA treatment also reduced the p-P38 and p-JNK protein level. However the protective effect of ATRA on CIR could be reversed by administration of retinoic acid alpha receptor antagonist Ro41-5253. SP600125 and SB203580, which is the JNK/P38 pathway inhibitors has the same protective effect as ATRA. These results indicated that ATRA may inhibit the JNK/P38 MAPK pathway to alleviate BBB disruption and improve CIR outcomes.
全反式视黄酸（ATRA）影响脑缺血再灌注（CIR）损伤的结局，但机制尚不清楚。本研究旨在探讨 ATRA 对 CIR 后血脑屏障（BBB）丧失的影响，并探讨可能的机制。通过对雄性 SD 大鼠进行短暂性大脑中动脉闭塞来构建体内 CIR 模型。在 CIR 后 24 小时检测神经功能缺损、BBB 通透性、脑水肿、MRI 和 JNK/P38 MAPK 蛋白。结果表明，ATRA 预处理可减轻 CIR 引起的神经功能缺损、BBB 通透性增加、梗死体积、紧密连接蛋白降解、抑制 MMP-9 蛋白表达和活性。ATRA 处理还降低了 p-P38 和 p-JNK 蛋白水平。然而，用视黄酸 α 受体拮抗剂 Ro41-5253 给予 ATRA 可逆转其对 CIR 的保护作用。JNK/P38 通路抑制剂 SP600125 和 SB203580 具有与 ATRA 相同的保护作用。这些结果表明，ATRA 可能通过抑制 JNK/P38 MAPK 通路来减轻 BBB 破坏并改善 CIR 结局。
