Department of Neurology, Xuzhou Tumor Hospital, Xuzhou, Jiangsu, 221005, China.
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, China.
Acta Biochim Pol. 2022 Nov 28;69(4):787-793. doi: 10.18388/abp.2020_6095.
Cerebral ischemia/reperfusion (I/R) injury is stimulated by blood restoration after ischemic stroke. Inflammatory response and inflammasome activation exerted vital functions in the development of cerebral I/R injury. miR-155-5p regulates inflammatory response in some diseases, while its role in inflammatory response and inflammasome activation of cerebral I/R injury development is unclear. Hence, the research focuses on investigating if miR-155-5p attenuate cerebral I/R injury via regulating inflammatory response and inflammasome activation and exploring the potential mechanism.
The oxygen-glucose deprivation/reoxygenation (OGD/R) model and the middle cerebral artery occlusion (MCAO) model were constructed. Cell viability and cytotoxicity were reflected by CCK-8 assay and LDH activity. The inflammatory cytokines secretion was determined using ELISA assay. Brain tissue infarction was evaluated using TTC staining.
miR-155-5p, Thioredoxin Interacting Protein (TXNIP) and NLR Family Pyrin Domain Containing 3 (NLRP3) were highly expressed in OGD/R model and MCAO rats. Knockdown of miR-155-5p alleviated cell injury, cell inflammation, and cell pyroptosis stimulated by OGD/R. Besides, miR-155-5p regulated TXNIP/NLRP3 pathway through modulating Dual-Specificity Phosphatase 14 (DUSP14) expression. Furthermore, knockdown of miR-155-5p improved brain tissue infarction and inhibited inflammation response and cell pyroptosis of MCAO rats.
Knockdown of miR-155-5p attenuated I/R inflammation and cell pyroptosis of cerebral via modulating DUSP14/TXNIP/NLRP3 pathway. These findings may provide a promising strategy to attenuate cerebral I/R injury.
脑缺血/再灌注（I/R）损伤是由缺血性中风后血液恢复引起的。炎症反应和炎性小体激活在脑 I/R 损伤的发展中发挥了重要作用。miR-155-5p 在一些疾病中调节炎症反应，但其在脑 I/R 损伤发展中的炎症反应和炎性小体激活中的作用尚不清楚。因此，本研究重点探讨 miR-155-5p 是否通过调节炎症反应和炎性小体激活来减轻脑 I/R 损伤，并探讨潜在的机制。
构建氧葡萄糖剥夺/复氧（OGD/R）模型和大脑中动脉闭塞（MCAO）模型。通过 CCK-8 测定法和 LDH 活性测定法反映细胞活力和细胞毒性。采用 ELISA 法测定炎症细胞因子的分泌。采用 TTC 染色评估脑组织梗死。
miR-155-5p、硫氧还蛋白相互作用蛋白（TXNIP）和 NOD 样受体家族含 pyrin 结构域 3（NLRP3）在 OGD/R 模型和 MCAO 大鼠中高表达。miR-155-5p 敲低可减轻 OGD/R 刺激的细胞损伤、细胞炎症和细胞焦亡。此外，miR-155-5p 通过调节双特异性磷酸酶 14（DUSP14）的表达来调节 TXNIP/NLRP3 通路。此外，miR-155-5p 敲低可改善 MCAO 大鼠的脑组织梗死，并抑制炎症反应和细胞焦亡。
miR-155-5p 敲低通过调节 DUSP14/TXNIP/NLRP3 通路减轻脑 I/R 炎症和细胞焦亡。这些发现可能为减轻脑 I/R 损伤提供一种有前途的策略。
