Qiao Yong, Peng Changliang, Li Ji, Wu Dongjin, Wang Xiuwen
Department of Spinal Surgery, The Second Hospital of Shandong University, Ji`nan, China.
Curr Neurovasc Res. 2018;15(3):211-219. doi: 10.2174/1567202615666180712153150.
This study was to investigate the neuroprotective effect of long noncoding RNAs Metastasis associated lung adenocarcinoma transcript-1 (lncRNA MALAT-1) in Spinal Cord Ischemic/Reperfusion Injury (SCIRI).
Quantitative real-time PCR (RT-qPCR) was used to examine the expressions of MALAT1, miR-204 and Bcl-2, while western blot was performed to examine Bcl-2. Besides, apoptosis was evaluated by the percentage of cell viability and apoptotic cells. Neurological evaluation was performed by measuring hindlimb locomotor function.
The expression of MALAT1 and Bcl-2 was decreased, while miRNA-204 (miR-204) was up-regulated in rats SCIRI model and neurocyte lines under hypoxic conditions. Oxygen, Glucose Deprivation (OGD) promoted apoptosis of neurocytes, downregulated MALAT1 and Bcl-2 and elevated miR-204 expression, however, overexpression of MALAT1 notably reversed this trend. Nevertheless, knockdown of MALAT1 increased cell apoptosis, decreased MALAT1 and Bcl-2 but upregulated miR-204. MALAT1 overexpression-induced anti-apoptosis and knockdowninduced pro-apoptosis were obviously reversed by synchronously overexpression and knockdown of miR-204, respectively. MALAT1-treated SCIRI rats exhibited lower Motor Deficit Index (MDI) scores, higher levels of MALAT1 and Bcl-2 expression and lower miR-204 expression.
Our data suggested that MALAT1 exerted neuroprotective effect in a rat model of SCIRI by regulating miR-204.
本研究旨在探讨长链非编码RNA转移相关肺腺癌转录本1（lncRNA MALAT-1）在脊髓缺血/再灌注损伤（SCIRI）中的神经保护作用。
采用定量实时PCR（RT-qPCR）检测MALAT1、miR-204和Bcl-2的表达，同时进行蛋白质免疫印迹法检测Bcl-2。此外，通过细胞活力和凋亡细胞百分比评估细胞凋亡情况。通过测量后肢运动功能进行神经学评估。
在大鼠SCIRI模型和缺氧条件下的神经细胞系中，MALAT1和Bcl-2的表达降低，而miRNA-204（miR-204）上调。氧糖剥夺（OGD）促进神经细胞凋亡，下调MALAT1和Bcl-2并提高miR-204表达，然而，MALAT1的过表达显著逆转了这一趋势。尽管如此，敲低MALAT1会增加细胞凋亡，降低MALAT1和Bcl-2但上调miR-204。MALAT1过表达诱导的抗凋亡和敲低诱导的促凋亡分别被miR-204的同步过表达和敲低明显逆转。用MALAT1处理的SCIRI大鼠表现出较低的运动功能障碍指数（MDI）评分、较高水平的MALAT1和Bcl-2表达以及较低的miR-204表达。
我们的数据表明，MALAT1通过调节miR-204在SCIRI大鼠模型中发挥神经保护作用。
