The Pathway of Let-7a-1/2-3p and HMGB1 Mediated Dexmedetomidine Inhibiting Microglia Activation in Spinal Cord Ischemia-Reperfusion Injury Mice
| Autor: | Qing-Tao Meng, Zhongyuan Xia, Ming Nuo, Ha Sen Ta Na |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Stimulation Pharmacology HMGB1 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Downregulation and upregulation medicine Animals HMGB1 Protein Cells Cultured Gene knockdown biology Microglia Chemistry Interleukin-6 Tumor Necrosis Factor-alpha General Medicine Analgesics Non-Narcotic Spinal cord medicine.disease Mice Inbred C57BL Microglial cell activation MicroRNAs 030104 developmental biology medicine.anatomical_structure Spinal Cord Reperfusion Injury biology.protein Reperfusion injury 030217 neurology & neurosurgery Dexmedetomidine |
| Zdroj: | Journal of molecular neuroscience : MN. 69(1) |
| ISSN: | 1559-1166 |
| Popis: | Microglial cell activation after spinal cord ischemia-reperfusion injury (SCIRI) commonly causes the secondary nerve motion function injury. This study aims to study the mechanism by which the drug dexmedetomidine (DEX) inhibits microglial cell activation and improves motion function of SCIRI mice. Mice SCIRI model was established, and microglia from spinal cord were isolated and cultured for subsequent molecule analysis of let-7a-1-3p, let-7a-2-3p, HMGB1, TNF-α, and IL-6. DEX was given by intraperitoneal injection. Mice motion function was evaluated by Basso mouse score. In vitro microglial cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to imitate ischemia-reperfusion injury stimulation. DEX injection improves the mouse motion function in SCIRI model and upregulates let-7a-1/2-3p expression in the isolated activated microglia from SCIRI mice. In OGD/R-stimulated microglia, DEX treatment also caused the inactivation of cells, the upregulation of let-7a-1/2-3p expression, and the downregulation of HMGB1 expression. While the co-silencing of let-7a-1/2-3p in microglia in addition to DEX treatment restored the activation of microglia. HMGB1 is a targeted gene for let-7a-1/2-3p and negatively regulated by them. HMGB1 knockdown abrogates the pro-activation impact on microglial cell by let-7a-1/2-3p silencing. DEX inhibits the activation of microglial cell in the spinal cord of SCIRI mice, mediated by the let-7a-1/2-3p/HMGB1 pathway. |
| Databáze: | OpenAIRE |
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