Dexmedetomidine protects PC12 cells from ropivacaine injury through miR-381/LRRC4 /SDF-1/CXCR4 signaling pathway

右美托咪啶通过miR-381/LRRC4/SDF-1/CXCR4信号通路保护罗哌卡因损伤的PC12细胞

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作者:Ying Xue, Tao Xu, Wei Jiang

Conclusions

Dexmedetomidine could protect PC12 cells from ropivacaine injury through miR-381/LRRC4/SDF-1/CXCR4 signaling pathway. This study may provide new therapeutic strategy targeting miR-381/LRRC4/SDF-1/CXCR4 signaling pathway about the prevention of ropivacaine induced neurocyte injury.

Methods

Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. Flow cytometry was used for assessing apoptosis. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and colony formation assays. Transwell assay was applied to measure the migration and invasion of cells. Dual luciferase reporter assay was applied for confirming the binding site between microRNA-381 (miR-381) and Leucine-rich repeat C4 protein (LRRC4).

Results

The viability of PC12 cells increased with raising the concentration of dexmedetomidine (0 μM, 10 μM, 50 μM, 100 μM). Dexmedetomidine reversed role of ropivacaine (0 mM, 0.1 mM, 0.5 mM, 1 mM) by upragulating the expression of miR-381 and suppressing the expression of LRRC4 in PC12 cells. miR-381 can directly interact with target gene LRRC4 and negatively regulate its expression. Dexmedetomidine promoted the proliferation, migration, and invasion and inhibited apoptosis of PC12 cells by suppressing LRRC4 via up-regulating the expressions of miR-381 and further activated SDF-1/CXCR4 signaling pathway. Conclusions: Dexmedetomidine could protect PC12 cells from ropivacaine injury through miR-381/LRRC4/SDF-1/CXCR4 signaling pathway. This study may provide new therapeutic strategy targeting miR-381/LRRC4/SDF-1/CXCR4 signaling pathway about the prevention of ropivacaine induced neurocyte injury.

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