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Biomed Pharmacother. 2018 Feb;98:63-68. doi: 10.1016/j.biopha.2017.11.142. Epub 2017 Dec 12.

Lin28a functionally modulates bupivacaine-induced dorsal root ganglion neuron apoptosis through TrkA activation.

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Department of Anesthesiology, Huangshi AiKang Hospital, Huangshi, 435000, China.
Department of Anesthesiology, People's Hospital of Shenzhen, Shenzhen, 518000, China.
Department of Anesthesiology, Huangshi Maternity and Children's Health Hospital, Edong Health care Group, 80 South Guilin Rd., Huangshi, 435000, China. Electronic address:



Lin-28 Homolog A gene (Lin28a) is an important regulator in nerve system. In this study, we investigated the functional mechanism of Lin28a during the process of bupivacaine (BUP)-induced neuronal apoptosis of spinal cord dorsal root ganglion neurons (DRGNs).


Young mouse DRGNs were cultured in vitro and treated with series concentrations of BUP. Apoptosis was evaluated by TUNEL assay. Corresponding Lin28a mRNA and protein expressions were evaluated by qRT-PCR and western blot (WB) assays. Lin28a was downregulated by siRNA and its effect on BUP (5 mM)-induced DRGN apoptosis was measured by qRT-PCR, WB and TUNEL assays, respectively. Alternatively, Lin28a was upregulated in DRGNs. It's effect on BUP (0.1 mM)-induced DRGN apoptosis was also measured. Finally, WB was used to examine Caspase-3/9 and TrkA protein expressions in Lin28a-downregualted and BUP-injured DRGN to explore Lin28a-associated signaling pathways.


In DRGN in vitro culture, 0.1 mM BUP induced moderate neuronal apoptosis while 5 mM BUP induced significant apoptosis. Lin28a mRNA and protein were both upregulated by BUP, in concentration-dependent manner. Functional assays showed that Lin28a downregulation rescued 5 mM BUP-induced neuronal apoptosis, whereas Lin28a upregulation aggravated 0.1 mM BUP-induced neuronal apoptosis in DRGNs. WB showed that Lin28a downregulation reduced Caspase-3/9 proteins and activated TrkA through phosphorylation in BUP-injured DRGNs.


Lin28a is a potent regulator in BUP-induced neuronal apoptosis in DRGNs. The apoptotic protection by Lin28a inhibition is likely through the activation of TrkA signaling pathway.


Apoptosis; Bupivacaine; DRGN; Lin28a; Neuron

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