CircOGDH通过调控miR-195-5p/PGAM5轴对氧糖剥夺/复糖复氧诱导的小胶质细胞损伤的影响

doi:10.3969/j.issn.1006-6233.2024.09.05

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Abstract Objective: To investigate the effect of circular RNA OGDH (CircOGDH) on microglia (MG) cell damage induced by oxygen-glucose deprivation/reoxygenation (OGD/R) by modulating the miR-195-5p/phosphoglycerate mutase 5 (PGAM5) axis.Methods: HMC3 cells cultured in vitro were separated into:NC group (normal culture), OGD/R, si-NC group, si-CircOGDH group, mimic NC group, miR-195-5p mimic group, si-CircOGDH+inhibitor NC group, and si-CircOGDH+miR-195-5p inhibitor group. Except for the NC group, the remaining groups constructed OGD/R models before transfecting the corresponding substances. QRT-PCR method was applied to determine the expression levels of CircOGDH, miR-195-5p, and PGAM5 mRNA. The levels of cell proliferation, apoptosis, reactive oxygen species (ROS), and inflammatory factors were measured in each group. Western blot was applied to detect the expression of Cleaved caspase-3 and Bax. Dual luciferase gene experiment was used to detect the targeting relationship between CircOGDH and miR-195-5p, and between PGAM5 and miR-195-5p.Results: Compared with the NC group, the expression of miR-195-5p and OD450 value were reduced in the OGD/R group, the mRNA expression of CircOGDH and PGAM5, apoptosis rate, ROS, and inflammatory cytokine levels, and the expression of Cleaved caspase-3 and Bax proteins were all elevated (P<0.05). Compared with the OGD/R group and the si-NC group, the expression of miR-195-5p and OD450 value were elevated in the si-CircOGDH group, the mRNA expression of CircOGDH and PGAM5, apoptosis rate, ROS and inflammatory cytokine levels, and the expression of Cleaved caspase-3 and Bax proteins were all reduced (P<0.05). Compared with the OGD/R group and the mimic NC group, the miR-195-5p mimic group showed no significant difference in CircOGDH (P>0.05), while the expression of miR-195-5p and OD450 values were increased, the expression of PGAM5 mRNA, apoptosis rate, ROS and inflammatory cytokine levels, and the expression of Cleaved caspase-3 and Bax protein were all reduced (P<0.05). Compared with the si-CircOGDH+inhibitor NC group, the CircOGDH of the si-CircOGDH+miR-195-5p inhibitor group was not significantly different (P>0.05), the expression of miR-195-5p and OD450 values were decreased, the expression of PGAM5 mRNA, apoptosis rate, ROS and inflammatory cytokine levels, and the expression of Cleaved caspase-3 and Bax protein were all elevated (P<0.05). A dual luciferase gene experiment showed that miR-195-5p had a targeting relationship with CircOGDH and PGAM5.Conclusion: Silencing CircOGDH can promote the proliferation of HMC3 cells induced by OGD/R, inhibit their inflammatory response and apoptosis, and may be related to the regulation of miR-195-5p/PGAM5 axis.

Key words： Circular RNA OGDH MiR-195-5p Phosphoglycerate mutase 5 Oxygen glucose deprivation/reoxygenation Microglia

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.09.05 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I9/1440

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