Jin Yan, Wei Fang, Dai Xiaoli, Qi Min, Ma Yukui
Shandong Provincial Key Laboratory of Chemical Drugs, Shandong Academy of Pharmaceutical Sciences, 250101, Jinan, China.
Shandong Freda Pharmaceutical Group Co., Ltd., 250101, Jinan, China.
Fundam Clin Pharmacol. 2018 Jun;32(3):270-278. doi: 10.1111/fcp.12348. Epub 2018 Mar 9.
This study aimed to investigate the anti-inflammatory effect of 4-methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF-α and IL-1β levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF-κB p65 subunit and expression of p-IκBα were investigated by Western blotting. Our results showed that 4-MCPC treatment decreased infarct volume significantly, compared with I/R group (16.8%±7.5% vs. 39.7%±10.9%); it reduced MPO activity (0.43 ± 0.10 vs. 1.00 ± 0.51 U/g) and expression levels of TNF-α (18.90 ± 3.65 vs. 35.87 ± 4.87 ng/g) and IL-1β (1.68 ± 0.23 vs. 2.67 ± 0.38 ng/g) in ischemic brain tissues of rats. Further study revealed that 4-MCPC treatment markedly reduced nuclear translocation of NF-κB p65 subunit and expression of p-IκBα in ischemic cerebral cortex. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury and displays anti-inflammatory actions through inhibition of the NF-κB signal pathway.
本研究旨在探讨4-甲基环十五烷酮（4-MCPC）对脑缺血/再灌注（I/R）损伤大鼠的抗炎作用。在本研究中，通过大脑中动脉闭塞（MCAO）2小时诱导大鼠局灶性脑缺血，并在再灌注前0.5小时用4-MCPC（8mg/kg）对大鼠进行治疗。在MCAO后24小时记录缺血梗死体积。此外，通过酶联免疫吸附测定法（ELISA）测定缺血性大脑皮层中的髓过氧化物酶（MPO）活性以及肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平，同时通过蛋白质印迹法研究核因子κB（NF-κB）p65亚基的核转位和磷酸化抑制蛋白κBα（p-IκBα）的表达。我们的结果表明，与I/R组相比，4-MCPC治疗显著降低了梗死体积（16.8%±7.5%对39.7%±10.9%）；它降低了MPO活性（0.43±0.10对1.00±0.51U/g）以及大鼠缺血脑组织中TNF-α（18.90±3.65对35.87±4.87ng/g）和IL-1β（1.68±0.23对2.67±0.38ng/g）的表达水平。进一步的研究表明，4-MCPC治疗显著减少了缺血性大脑皮层中NF-κB p65亚基的核转位和p-IκBα的表达。综上所述，我们的结果表明，4-MCPC可预防脑I/R损伤，并通过抑制NF-κB信号通路发挥抗炎作用。
