Xiao Peng, Zhang Xiaoming, Li Yanfei, Ma Zhongyi, Si Shuping, Gao Xinxue
Department of Psychiatry, Jining Psychiatric Hospital, Jining, Shandong 272051, P.R. China.
Exp Ther Med. 2020 Jan;19(1):551-556. doi: 10.3892/etm.2019.8228. Epub 2019 Nov 21.
Effects of micro ribonucleic acid (miR)-9 on neuronal apoptosis and expression levels of apoptosis genes B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in depression model rats, as well as its regulatory mechanism, were investigated. Thirty Sprague-Dawley rats were randomly divided into control group (n=10), model group (n=10) and miR-9 inhibitor group (n=10). The rat model of depression was established using the chronic stress method. The learning and memory abilities of rats were detected via water maze test, the neuronal morphology of the brain was detected using hematoxylin and eosin (H&E) staining, and the levels of serum Bcl-2 and Bax were determined using the enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the neuronal apoptosis in the brain was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein levels of Notch1 and Hes1 in brain tissues were measured via western blot analysis. Compared with the control group, the rats in the model group presented significantly decreased learning and memory abilities, poor neuronal morphology of the brain, significantly higher neuronal apoptosis rate in the brain, decreased level of serum Bcl-2, increased level of serum Bax, and significantly decreased protein levels of Notch1 and Hes1 in brain tissues. Compared with the model group, the rats in miR-9 inhibitor group showed obviously improved learning and memory abilities, improved neuronal morphology of the brain, an obviously lower neuronal apoptosis rate in the brain, increased level of serum Bcl-2, decreased level of serum Bax, and obviously increased protein levels of Notch1 and Hes1 in brain tissues. In conclusion, miR-9 inhibitor can promote the neurological function recovery and inhibit the neuronal apoptosis of depression model rats through activating the Notch signaling pathway, suggesting that miR-9 can be an important therapeutic target for depression.
研究了微小核糖核酸（miR）-9对抑郁模型大鼠神经元凋亡及凋亡相关基因B细胞淋巴瘤-2（Bcl-2）和Bcl-2相关X蛋白（Bax）表达水平的影响及其调控机制。将30只Sprague-Dawley大鼠随机分为对照组（n = 10）、模型组（n = 10）和miR-9抑制剂组（n = 10）。采用慢性应激法建立大鼠抑郁模型。通过水迷宫试验检测大鼠的学习记忆能力，用苏木精-伊红（H&E）染色检测大脑神经元形态，使用酶联免疫吸附测定（ELISA）试剂盒测定血清Bcl-2和Bax水平。此外，通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）试验检测大脑中的神经元凋亡，并通过蛋白质印迹分析测量脑组织中Notch1和Hes1的蛋白水平。与对照组相比，模型组大鼠的学习记忆能力显著下降，大脑神经元形态较差，大脑神经元凋亡率显著升高，血清Bcl-2水平降低，血清Bax水平升高，脑组织中Notch1和Hes1的蛋白水平显著降低。与模型组相比，miR-9抑制剂组大鼠的学习记忆能力明显改善，大脑神经元形态改善，大脑神经元凋亡率明显降低，血清Bcl-2水平升高，血清Bax水平降低，脑组织中Notch1和Hes1的蛋白水平明显升高。综上所述，miR-9抑制剂可通过激活Notch信号通路促进抑郁模型大鼠神经功能恢复并抑制神经元凋亡，提示miR-9可能是抑郁症的一个重要治疗靶点。
