| 职 瑾,段 斌,王 静,王 清,王虎清.miR-124与MAPK/ERK通路对调节脑梗死大鼠神经细胞凋亡的影响[J].现代生物医学进展英文版,2021,(12):2235-2240. |
| miR-124与MAPK/ERK通路对调节脑梗死大鼠神经细胞凋亡的影响 |
| Effects of miR-124 and MAPK/ERK Pathway on Neuronal Apoptosis in Rats with Cerebral Infarction |
| Received:December 09, 2020 Revised:January 05, 2021 |
| DOI：10.13241/j.cnki.pmb.2021.12.008 |
| 中文关键词: miR-124 MAPK/ERK信号通路 脑梗死 神经细胞凋亡 |
| 英文关键词: miR-124 MAPK/ERK signaling pathway Cerebral infarction Neuronal apoptosis |
| 基金项目:陕西省自然科学基础研究计划项目（2017JM8142）；西安市科技计划项目（2019114613YX001SF039(6)） |
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| 中文摘要: |
| 摘要 目的：研究miR-124和MAPK/ERK途径对脑梗死大鼠神经细胞凋亡的影响及其可能的机制。方法：本研究将SD大鼠随机分为假手术组（Sham组）、模型组（CI组）、miR-124组（miR组）、脑梗死+miR-124组（CI+miR组）和脑梗死+MEK/ERK阻滞剂组（CI+U0126组），采用mNSS评分法评估大鼠神经功能损伤程度，采用TTC染色检测脑梗死体积，采用尼式染色检查脑组织的病理情况，采用TUNEL染色法检测大鼠脑神经细胞凋亡，TRIzol法提取总RNA，RT-PCR检测miR-124、ERK1和ERK2基因表达，蛋白质免疫印迹法检测Caspase-3、Bax、Bcl-2、MEK2和ERK1蛋白表达水平。结果：与Sham组和miR组相比，CI组、CI+miR组和CI+U0126组大鼠的脑梗死体积、mNSS评分和脑含水量均显著增加（P<0.01）。Sham组、miR组、CI+miR组和CI+U0126组大鼠的脑组织中尼式体的数量显著高于CI组，模型组大鼠的脑神经元结构被破坏且出现核移位和细胞坏死等病理变化；与Sham组和miR组相比，CI组大鼠中miR-124的表达水平显著降低（P<0.01），CI+miR组和CI+U0126组大鼠中miR-124的表达水平显著上调（P<0.01）。TUNEL染色结果显示，与模型组相比，CI+miR组和CI+U0126组大鼠中凋亡数量显著减少（P<0.01），ERK1和ERK2的mRNA相对表达水平均显著下调（P<0.01）。与模型组相比，CI+miR组和CI+U0126组大鼠脑组织中Caspase-3和Bax蛋白表达水平显著下调，Bcl-2蛋白的表达水平显著上调（P<0.01）。与模型组相比，CI+miR组和CI+U0126组大鼠脑组织中磷酸化的p-MEK-2和p-ERK1/2蛋白表达水平均显著下调（P<0.01）。结论：miR-124可能通过抑制MAPK/ERK信号通路的激活，减少脑梗死大鼠的神经细胞的凋亡，最终发挥保护作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of miR-124 and MAPK/ERK pathways on neuronal apoptosis in rats with cerebral infarction and the possible underlying mechanisms. Methods: In this experiment, SD rats were randomly divided into a sham operation group (sham group), a cerebral infarction group (CI group), miR-124 group (miR group), a CI+miR-124 group (CI+miR group) and cerebral infarction+MEK/ERK blocker group (CI+U0126 group). The mNSS scoring method was used to evaluate the degree of neurological damage in rats. The cerebral infarction volume and pathological conditions of rat brain tissue were detected by TTC staining and Nissl staining, respectively. TUNEL staining was used to detect rat brain neuronal apoptosis, TRIzol method was used to extract total RNA, RT-PCR was used to detect miR-124, ERK1 and ERK2 gene expression, and Western blot was used to detect Caspase-3, Bax, Bcl-2, MEK2 and ERK1 protein expression. Results: Compared with the sham group and miR group, the cerebral infarct volume, mNSS score and brain water content of the CI group, CI+miR group and CI+U0126 group increased significantly(P<0.01). The results of Nissl staining of rat brain tissue showed that the number of Nissl's body of rats in the sham group, miR group, CI+miR group and CI+U0126 group was higher than CI group, and the brain neuron structure of the CI group was destroyed and showed nuclear shift and cell pathological changes such as necrosis. Compared with Sham group and miR group, the expression level of miR-124 in CI group rats was significantly reduced, while the miR-124 expression level in rats of the CI+miR group and CI+U0126 group were significantly up-regulated (P<0.01). The results of TUNEL staining showed that compared with the CI group, the number of apoptosis in rats in the CI+miR group and CI+U0126 group was significantly reduced(P<0.01), and the relative expression levels of ERK1 and ERK2 mRNA were significantly down-regulated(P<0.01). Compared with the CI group, the relative expression level of Caspase-3 and Bax protein in the brain tissue of the CI+miR group and CI+U0126 group was significantly down-regulated, and the relative expression level of Bcl-2 protein was significantly up-regulated(P<0.01). Compared with the CI group, the relative protein expression level of phosphorylated p-MEK-2 and p-ERK1/2 in the brain tissue of the CI+miR group and CI+U0126 group was significantly down-regulated(P<0.01). Conclusion: miR-124 might inhibit the activation of MAPK/ERK signaling pathway, reduce neuronal apoptosis in rats with cerebral infarction, and finally play a protective role. |
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