Liu Jia, Jiang Xiaowen, Zhang Qiao, Lin Sen, Zhu Jun, Zhang Yajun, Du Jiabao, Hu Xiaolong, Meng Weihong, Zhao Qingchun
Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110840, China; Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
Neurochem Int. 2017 Jul;107:191-197. doi: 10.1016/j.neuint.2016.12.024. Epub 2017 Jan 12.
Kukoamine A (KuA) is a bioactive compound, which is known for a hypotensive effect. Recent studies have shown that KuA has anti-oxidative effect and anti-apoptosis stress in vitro. However, its neuroprotective effect in rats with cerebral ischemia is still unclear. In the study, we investigated whether KuA could attenuate cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO) in rats. Results revealed that KuA could significantly reduce infarct volume both pre-treatment and post-treatment, and increase corresponding Garcia neurological scores. Acute KuA postconditioning not only significantly reduced cerebral infarct volume, brain water content and improved neurological deficit scores, but also decreased the number of TUNEL-positive cells. Moreover, it markedly increased the activities of Cu/Zn-SOD and Mn-SOD, reduced levels of MDA and HO Increased expressions of caspase-3, cytochrome c and the ratio of Bax/Bcl-2 were significantly alleviated with KuA treatment. These findings demonstrated that KuA was able to protect the brain against injury induced by pMCAO via mitochondria mediated apoptosis signaling pathway.
苦柯胺A（KuA）是一种生物活性化合物，以其降压作用而闻名。最近的研究表明，KuA在体外具有抗氧化作用和抗凋亡应激作用。然而，其对大脑缺血大鼠的神经保护作用仍不清楚。在本研究中，我们调查了KuA是否能减轻大鼠永久性大脑中动脉闭塞（pMCAO）诱导的脑缺血。结果显示，预处理和后处理时KuA均可显著减少梗死体积，并提高相应的加西亚神经学评分。急性KuA后处理不仅显著减少了脑梗死体积、脑含水量并改善了神经功能缺损评分，还减少了TUNEL阳性细胞数量。此外，它显著增加了铜/锌超氧化物歧化酶（Cu/Zn-SOD）和锰超氧化物歧化酶（Mn-SOD）的活性，降低了丙二醛（MDA）水平和血红素加氧酶（HO）水平。KuA处理显著减轻了半胱天冬酶-3（caspase-3）、细胞色素c的表达增加以及Bax/Bcl-2比值升高。这些发现表明，KuA能够通过线粒体介导的凋亡信号通路保护大脑免受pMCAO诱导的损伤。
