Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, China.
Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639, Longmian Road, Nanjing, 211198, China.
J Mol Neurosci. 2018 Jul;65(3):391-399. doi: 10.1007/s12031-018-1063-9. Epub 2018 Jul 4.
Ischemic stroke is one of the most dangerous acute diseases which causes death or deformity. Apoptosis has been shown to play an important role in the development and pathogenesis of cerebral ischemia-reperfusion injury (I/R injury), but the related mechanism is unclear. Levo-tetrahydropalmatine (L-THP), a bioactive ingredient extracted from the Chinese herb Corydalis, can penetrate the blood-brain barrier and exert various pharmacological effects on neural tissues. The present study examined the neuroprotective effect of L-THP on neuronal apoptosis induced by cerebral I/R injury. Results showed that pretreatment with L-THP (12.5, 25, and 50 mg/kg) improved neurological outcomes and reduced infarct volume and cerebral edema in comparison with the brains of the middle cerebral artery occlusion (MCAO) group. These findings provided evidence for the neuroprotective effects of L-THP against cerebral I/R injury. Furthermore, administration of L-THP enhanced the expression of Bcl-2 and attenuated the content of Bax, cleaved caspase-3, and PARP. L-THP could improve the reduction of NeuN-positive cells induced by I/R injury. These results suggested that L-THP could inhibit neuroapoptosis in cerebral ischemic rats. c-Abl was discovered as the critical protein responsible for neurocyte apoptosis; however, few data have been published on the relation between ischemic stroke and the expression of c-Abl. We found that both c-Abl expression and neuronal apoptosis were significantly increased in the MCAO group, while pretreatment with L-THP could ameliorate this effect. Therefore, we deduced that reduced c-Abl overexpression may play a role in the anti-apoptosis effect of L-THP after cerebral I/R injury. Thus, L-THP may provide a potential therapeutic approach for the treatment of ischemic stroke. Graphical Abstract ᅟ.
缺血性脑卒中是导致死亡或残疾的最危险的急性疾病之一。细胞凋亡在脑缺血再灌注损伤（I/R 损伤）的发生和发病机制中起重要作用，但相关机制尚不清楚。左旋延胡索乙素（L-THP）是从中国草药延胡索中提取的一种生物活性成分，可穿透血脑屏障，对神经组织发挥多种药理作用。本研究探讨了 L-THP 对脑 I/R 损伤诱导的神经元凋亡的神经保护作用。结果表明，与大脑中动脉闭塞（MCAO）组相比，L-THP（12.5、25 和 50mg/kg）预处理可改善神经功能，并减少梗死体积和脑水肿。这些发现为 L-THP 对脑 I/R 损伤的神经保护作用提供了证据。此外，L-THP 给药增强了 Bcl-2 的表达，并减弱了 Bax、裂解的 caspase-3 和 PARP 的含量。L-THP 可以改善 I/R 损伤引起的 NeuN 阳性细胞减少。这些结果表明，L-THP 可以抑制脑缺血大鼠的神经细胞凋亡。c-Abl 被发现是负责神经细胞凋亡的关键蛋白；然而，关于缺血性脑卒中与 c-Abl 表达之间的关系，发表的数据很少。我们发现，MCAO 组中 c-Abl 表达和神经元凋亡均显著增加，而 L-THP 预处理可改善这种作用。因此，我们推断 c-Abl 过表达减少可能在 L-THP 脑 I/R 损伤后发挥抗凋亡作用。因此，L-THP 可能为缺血性脑卒中的治疗提供一种潜在的治疗方法。
