Zhang Yi, Yin Jie, Zhang Lang, Qi Chu-Chu, Ma Ze-Lin, Gao Li-Ping, Wang De-Gui, Jing Yu-Hong
a Department of Neurology , People Hospital of Gansu Province , Lanzhou , P.R. China.
b School of Basic Medical Sciences, Institute of Anatomy and Histology & Embryology, Neuroscience , Lanzhou University , Lanzhou , P.R. China.
Neurol Res. 2017 Mar;39(3):248-258. doi: 10.1080/01616412.2017.1283830. Epub 2017 Jan 23.
Ischemic precondition plays a protective effect during cerebral ischemia. This effect partly depends on the autophagic activity. However, whether the activity of autophagy can exert the protective effects after cerebral ischemia is unclear. In this study, rats were treated with spermidine, an activator of autophagy, and injected with sodium laurate via the internal carotid artery to stimulate cerebral small vessel disease (CSVD). The effects of the spermidine precondition on brain injury were evaluated by behavioural test, histology assay, ultrastructure observation, and autophagic-related signals. Furthermore, the mitochondria of brain tissue were isolated, and mitDNA were extracted. The stability of mitDNA was analyzed by quantitative real-time PCR. Results showed that the penetrating artery of the striatum was damaged. This damage was accompanied by neural inflammation characterized by an increase in Fluoro-Jade C (FJC)-positive cells after sodium laurate injection. Spermidine pretreatment decreased the deletion of mitDNA and the autophagy hyperactivity induced by the laurate injection. Likewise, spermidine reduced the neurological deficit and FJC reactivation of striatum at 48 h after laurate injection. These results suggested sodium laurate injection through the internal carotid artery can induce the pathological features of CSVD characterized by the damage of penetrating artery, neurological deficit, mitochondrial impairment, and autophagic hyperactivity. Pretreatment with spermidine can ameliorate these outcomes. Further study indicated that the protective effect of the spermidine precondition is associated with the maintenance of mitochondrial stability and proper autophagy activity.
缺血预处理在脑缺血期间发挥保护作用。这种作用部分取决于自噬活性。然而，自噬活性在脑缺血后是否能发挥保护作用尚不清楚。在本研究中，用自噬激活剂亚精胺处理大鼠，并通过颈内动脉注射月桂酸钠以诱发脑小血管病（CSVD）。通过行为测试、组织学分析、超微结构观察和自噬相关信号评估亚精胺预处理对脑损伤的影响。此外，分离脑组织的线粒体并提取线粒体DNA（mitDNA）。通过定量实时PCR分析mitDNA的稳定性。结果显示纹状体的穿通动脉受损。这种损伤伴随着神经炎症，表现为注射月桂酸钠后氟玉红C（FJC）阳性细胞增加。亚精胺预处理减少了mitDNA的缺失以及月桂酸钠注射诱导的自噬亢进。同样，亚精胺在注射月桂酸钠后48小时减少了纹状体的神经功能缺损和FJC再激活。这些结果表明，通过颈内动脉注射月桂酸钠可诱发以穿通动脉损伤、神经功能缺损、线粒体损伤和自噬亢进为特征的CSVD病理特征。亚精胺预处理可改善这些结果。进一步研究表明，亚精胺预处理的保护作用与线粒体稳定性的维持和适当的自噬活性有关。
