Abstract:Objective: To investigate the effect of long non-coding RNA (LncRNA) KCNQ1OT1 on neurological function of intracerebral hemorrhage (ICH) model rats by adjusting microRNA-214-3p/N-myc downstream regulated gene 3 (miR-214-3p/NDRG3) axis. Methods: SD rats were assigned into sham surgery group (Sham), ICH group, LncRNA KCNQ1OT1 interference plasmid control (sh-NC) group, LncRNA KCNQ1OT1 interference plasmid (sh-KCNQ1OT1) group, sh-KCNQ1OT1+miR-214-3p inhibitor control (miR-In-NC) group, and sh-KCNQ1OT1+miR-214-3p inhibitor (miR-214-3p-In) group, each with 12 rats. The modified neurological severity score (mNSS) was used to assess changes in neurological function. The volume of cerebral hematoma in each group was measured. HE staining was performed to observe the pathological changes in brain tissue. TUNEL staining was used to observe cell apoptosis in brain tissue. The changes in the expression level of NDRG3 were observed by immunohistochemical staining. ELISA was used to detect the levels of TNF-α and IL-1β in the rat brain tissue. qRT-PCR was used to detect the levels of LncRNA KCNQ1OT1, miR-214-3p, and NDRG3 mRNA in the brain tissues. Western blot was performed to detect the expression of NDRG3, Bax, and Bcl-2 proteins in the brain tissues. Dual luciferase reporter gene assay was used to determine the targeting relationship between miR-214-3p and LncRNA KCNQ1OT1 or NDRG3. Results: For Sham group, the mNSS score, cerebral hematoma volume, and brain tissue apoptosis rate of rats in ICH group unusually increased (P<0.05), the brain tissue structure was disrupted, the numbers of red blood cells, inflammatory cell infiltration, and glial cells increased, the TNF-α, IL-1β, LncRNA KCNQ1OT1, NDRG3, and Bax in brain tissue were unusually increased (P<0.05), and the miR-214-3p and Bcl-2 were greatly reduced (P<0.05). For sh-NC group, the mNSS score cerebral hematoma volume, and brain tissue apoptosis rate of rats in sh-KCNQ1OT1 group greatly reduced (P<0.05), the brain tissue structure was restored, the numbers of red blood cells, inflammatory cell infiltration, and glial cells declined, the TNF-α, IL-1β, LncRNA KCNQ1OT1, NDRG3, and Bax in brain tissue were unusually declined (P<0.05), and the miR-214-3p and Bcl-2 were greatly raised (P<0.05). For sh-KCNQ1OT1+miR-In-NC group, the mNSS score, cerebral hematoma volume, and brain tissue apoptosis rate of rats in sh-KCNQ1OT1+miR-214-3p-In group greatly raised (P<0.05), the brain tissue structure was disrupted, the numbers of red blood cells, inflammatory cell infiltration, and glial cells raised, the TNF-α, IL-1β, NDRG3, and Bax in brain tissue were greatly raised (P<0.05), and the miR-214-3p and Bcl-2 were greatly reduced (P<0.05). Compared with the miR-NC group, the relative luciferase activity of cells transfected with KCNQ1OT1-WT or NDRG3-WT in the miR-214-3p group was significantly decreased. (P<0.05). Conclusion: Downregulation of LncRNA KCNQ1OT1 may alleviate neurological dysfunction in ICH rats by adjusting miR-214-3p/NDRG3 axis.
高小恒, 刘一鑫, 耿炜, 张瑜, 马岩朋, 周涛. LncRNA KCNQ1OT1调控miR-214-3p/NDRG3轴对脑出血模型大鼠神经功能的影响[J]. 河北医学, 2025, 31(12): 2004-2013.
GAO Xiaoheng, et al. Effect of LncRNA KCNQ1OT1 on Neurological Function of Rats with Cerebral Hemorrhage Model by Adjusting miR-214-3p/NDRG3 Axis. HeBei Med, 2025, 31(12): 2004-2013.