East Section of South Second Ring Road, The Second Affiliated Hospital of Xi'an Jiaotong University, No.151, Xi'an 710054, Shaanxi, China.
Ninth Hospital of Xi'an Affiliated To Xi'an Jiaotong University, Xi'an 710054, China.
Neurotox Res. 2022 Feb;40(1):44-55. doi: 10.1007/s12640-021-00457-4. Epub 2022 Jan 11.
In recent years, orexin (ORX) and melanin-concentrating hormone (MCH) have been demonstrated to exert neuroprotective roles in cerebral ischemia. Hence, this study investigated the regulatory function of ORX and MCH in neurological function following ischemic stroke and explored the molecular mechanism underlying these functions. A rat model of ischemic stroke was developed by middle cerebral artery occlusion (MCAO), and Longa scoring was employed to evaluate the degree of neurological function deficit. The expression patterns of ORX and MCH were examined by real-time polymerase chain reaction in the brain tissues of rats with ischemic stroke induced by middle cerebral artery occlusion (MCAO). Moreover, electroencephalography (EEG) analysis and high-performance liquid chromatography (HPLC) were respectively performed to detect rapid-eye movement (REM) sleep, the glutamate (Glu) uptake, and the expression of γ-aminobutyric acid B receptor (GABA). Immunoblotting was performed to test the levels of autophagic markers LC3, BECLIN-1, and p62. Immunohistochemistry (IHC) staining and TUNEL assays were respectively used to assess the autophagy and neuronal apoptosis. Results demonstrated that ORX and MCH were lowly expressed in brain of rats with ischemic stroke. ORX or MCH overexpression decreased neuronal apoptosis and autophagy, and improved the sleep architecture of post-stroke rats, while rescuing Glu uptake and GABA expression. ORX or MCH upregulation exerted protective effects on neurological function. Taken together, ORX and/or MCH protect against ischemic stroke in a rat model, highlighting their value as targets for the clinical treatment of ischemic stroke.
近年来，食欲素（ORX）和黑色素浓缩激素（MCH）已被证明在脑缺血中发挥神经保护作用。因此，本研究探讨了 ORX 和 MCH 在缺血性中风后神经功能中的调节作用，并探讨了这些功能的潜在分子机制。通过大脑中动脉闭塞（MCAO）建立大鼠缺血性中风模型，并采用 Longa 评分评估神经功能缺损程度。通过实时聚合酶链反应检测大脑中动脉闭塞（MCAO）诱导的缺血性中风大鼠脑组织中 ORX 和 MCH 的表达模式。此外，分别进行脑电图（EEG）分析和高效液相色谱（HPLC）检测快速眼动（REM）睡眠、谷氨酸（Glu）摄取以及γ-氨基丁酸 B 受体（GABA）的表达。通过免疫印迹检测自噬标志物 LC3、BECLIN-1 和 p62 的水平。免疫组织化学（IHC）染色和 TUNEL 检测分别用于评估自噬和神经元凋亡。结果表明，ORX 和 MCH 在缺血性中风大鼠脑内表达水平较低。ORX 或 MCH 的过表达可减少神经元凋亡和自噬，并改善中风后大鼠的睡眠结构，同时恢复 Glu 摄取和 GABA 表达。ORX 或 MCH 的上调对神经功能具有保护作用。总之，ORX 和/或 MCH 可减轻大鼠缺血性中风模型的损伤，提示它们可能成为缺血性中风临床治疗的靶点。
