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Neurons employ different pathways to repair DNA damage. However, the mechanism underlying bupivacaine\u2010mediated DNA damage repair is unclear. A rat neuronal injury model was established by intrathecal injection of (3%) bupivacaine. An in vitro neuronal injury model was generated by exposing SH\u2010SY5Y cells to bupivacaine (1.5\u2009mmol\/L). Then, a cDNA plate array was used to identify the DNA repair genes after bupivacaine exposure. The results showed that xeroderma pigmentosum complementary group D (XPD) of the nuclear excision repair (NER) pathway was closely associated with the repair of DNA damage induced by bupivacaine. Subsequently, Western blot assay and immunohistochemistry indicated that the expression of the repair enzyme XPD was upregulated after DNA damage. Downregulation of XPD expression by a lentivirus aggravated the DNA damage induced by bupivacaine. In addition, phosphatidyl\u20103\u2010kinase (PI3K)\/AKT signaling in neurons was inhibited after exposure to bupivacaine. After PI3K\/AKT signaling was inhibited, bupivacaine\u2010mediated DNA damage was further aggravated, and the expression of XPD was further upregulated. However, knockdown of XPD aggravated bupivacaine\u2010mediated neuronal injury but did not affect PI3K\/AKT signaling. In conclusion, the repair enzyme XPD, which was partially regulated by PI3K\/AKT signaling, responded to bupivacaine\u2010mediated neuronal DNA damage. These results can be used as a reference for the treatment of bupivacaine\u2010induced neurotoxicity.<\/jats:p>","DOI":"10.1155\/2021\/9925647","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T15:39:47Z","timestamp":1633880387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The DNA Repair Enzyme XPD Is Partially Regulated by PI3K\/AKT Signaling in the Context of Bupivacaine\u2010Mediated Neuronal DNA 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