目的：验证长链非编码RNA（LncRNA）MALAT1是否参与脑梗死的神经元损伤，并探讨MALAT1在
其中的影响机制。方法：通过氧糖剥夺（OGD）/复氧（R）)构建脑梗死细胞模型，使用CCK-8检测细胞活力；
流式细胞术分析细胞凋亡率；ELISA检测炎症相关因子[肿瘤坏死因子α（TNF-α）、白介素-6（IL-6）] 水平；
Western blot检测凋亡相关蛋白（Bax、Bcl-2）的含量；RT-qPCR 检测MALAT1和miRNA-125b的表达水平；双
荧光素酶检测报告基因试验检测MALAT1和miRNA-125b之间的调控关系；CO-IP检测P35与CDK5之间
的结合。结果：成功建立了OGD/R细胞模型，且与Control组相比，OGD/R组中MALAT1的表达显著降低；
过表达MALAT1后，神经元细胞的活力上升，凋亡水平降低，TNF-α、IL-6、Bax、P25的水平显著降低，Bcl-2、
P35的水平显著上升；进一步实验表明MALAT1负向调控miRNA-125b的表达，添加miRNA-125b模拟物可
以逆转过表达MALAT1对OGD/R细胞的作用，但P35的表达进一步增加，P25的表达则进一步减少。结论：
MALAT1通过抑制miRNA-125b的表达调控P35-CDK5改善脑梗死导致的神经元损伤。
To verify whether long non-coding RNA (lncRNA) MALAT1 participates in neuronal
injury after cerebral infarction, and to explore the underlying mechanism of MALAT1. Methods: An in vitro
cellular model of cerebral infarction was established by oxygen-glucose deprivation/reoxygenation (OGD/R).
Cell viability was measured using the CCK-8 assay. Flow cytometry was applied to analyze the cell apoptosis
rate. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammation-related factors
including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was performed to detect the
expression of apoptosis-related proteins (Bax, Bcl-2). RT-qPCR was adopted to quantify the expression levels of
MALAT1 and miR-125b. Dual-luciferase reporter assay was used to verify the regulatory interaction between
MALAT1 and miR-125b. Co-immunoprecipitation (Co-IP) was utilized to detect the binding between P35 and
CDK5. Results: The OGD/R cell model was successfully established. Compared with the Control group,
MALAT1 expression was significantly downregulated in the OGD/R group. After overexpression of MALAT1,
neuronal viability was increased, the apoptosis level was decreased; the levels of TNF-α, IL-6, Bax and P25 were
markedly reduced, whereas the levels of Bcl-2 and P35 were significantly elevated. Further experiments
demonstrated that MALAT1 negatively regulated miR-125b expression. The addition of miR-125b mimic
reversed the protective effects of MALAT1 overexpression in OGD/R-treated neurons; meanwhile, the
expression of P35 was further increased and P25 expression was further decreased. Conclusion: MALAT1
ameliorates cerebral infarction-induced neuronal injury by inhibiting miR-125b to regulate the P35-CDK5
pathway.
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