Clinical Research Center, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, Hainan 570203, P.R. China.
Hainan Clinical Research Center for Preventive Treatment of Diseases, Hainan Provincial Hospital of Traditional Chinese Medicine, Haikou, Hainan 570203, P.R. China.
Mol Med Rep. 2023 Apr;27(4). doi: 10.3892/mmr.2023.12972. Epub 2023 Mar 3.
Blood‑brain barrier (BBB) damage is one of the main causes of poor outcomes and increased mortality rates following cerebral ischemia‑reperfusion injury. Apolipoprotein E (ApoE) and its mimetic peptide have been previously reported to exhibit potent neuroprotective properties in various central nervous system disease models. Therefore, the present study aimed to investigate the possible role of the ApoE mimetic peptide COG1410 in cerebral ischemia‑reperfusion injury and its potential underlying mechanism. Male SD rats were subjected to 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Evans blue leakage and IgG extravasation assays results revealed that COG1410 treatment significantly reduced BBB permeability. In addition, zymography and western blotting were used to prove that COG1410 was able to downregulate the activities of MMPs and upregulate the expression of occludin in the ischemic brain tissue samples. Subsequently, COG1410 was found to significantly reverse microglia activation while also suppressing inflammatory cytokine production, according to immunofluorescence signal of Iba‑1 and CD68 and protein expression of COX‑2. Consequently, this neuroprotective mechanism mediated by COG1410 was further tested using the BV2 cell line , which was exposed to oxygen glucose deprivation followed by reoxygenation. The mechanism of COG1410 was found to be mediated, as least partly, through the activation of triggering receptor expressed on myeloid cells 2. In conclusion, the data suggest that COG1410 can alleviate BBB injury and neuroinflammation following ischemic stroke.
血脑屏障（BBB）损伤是脑缺血再灌注损伤后预后不良和死亡率增加的主要原因之一。载脂蛋白 E（ApoE）及其模拟肽先前已被报道在各种中枢神经系统疾病模型中具有强大的神经保护作用。因此，本研究旨在探讨 ApoE 模拟肽 COG1410 在脑缺血再灌注损伤中的可能作用及其潜在机制。雄性 SD 大鼠接受 2 小时大脑中动脉闭塞，随后再灌注 22 小时。伊文思蓝渗漏和 IgG 渗出测定结果表明，COG1410 治疗可显著降低 BBB 通透性。此外，通过明胶酶谱和 Western blot 证明 COG1410 能够下调 MMPs 的活性并上调缺血脑组织样本中 occludin 的表达。随后，根据 Iba-1 和 CD68 的免疫荧光信号和 COX-2 的蛋白表达，发现 COG1410 能够显著逆转小胶质细胞激活并抑制炎性细胞因子的产生。因此，通过用氧葡萄糖剥夺再氧合处理 BV2 细胞系进一步测试了 COG1410 的这种神经保护机制。COG1410 的作用机制被发现至少部分是通过髓样细胞表达的触发受体 2 的激活介导的。总之，数据表明 COG1410 可以减轻缺血性中风后 BBB 损伤和神经炎症。
