Analysis of the long non-coding RNA and mRNA expression profiles associated with lidocaine-induced neurotoxicity in the spinal cord of a rat model

Zhong Zhang; Yanping Jian; Lei Wu; Yanan Cao; Longyan Li; Qulian Guo; E Wang; Qian Li

doi:10.1016/j.neuro.2022.03.002

Analysis of the long non-coding RNA and mRNA expression profiles associated with lidocaine-induced neurotoxicity in the spinal cord of a rat model

Neurotoxicology. 2022 May:90:88-101. doi: 10.1016/j.neuro.2022.03.002. Epub 2022 Mar 10.

Authors

Zhong Zhang¹, Yanping Jian², Lei Wu³, Yanan Cao¹, Longyan Li¹, Qulian Guo¹, E Wang¹, Qian Li⁴

Affiliations

¹ Department of Anesthesiology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, 410008 Changsha City, Hunan Province, China.
² Department of Anesthesiology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, 410008 Changsha City, Hunan Province, China; Department of Anesthesiology, Marine Corps Hospital of PLA, No. 1 Xinyang Road, 521000 Chaozhou City, Guangdong Province, China.
³ Department of Anesthesiology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, 410008 Changsha City, Hunan Province, China; Department of Anesthesiology, Hunan Children's Hospital, No. 86 Ziyuan Road, 410007 Changsha City, Hunan Province, China.
⁴ Department of Anesthesiology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, 410008 Changsha City, Hunan Province, China. Electronic address: liqianxyane@163.com.

PMID: 35283115
DOI: 10.1016/j.neuro.2022.03.002

Abstract

Neurotoxicity is thought to be one of the causes of lidocaine-associated neurological complications; however, the mechanisms underlying lidocaine-related neurotoxicity are still unclear. Long non-coding RNAs (lncRNAs) are novel mediators of neurotoxicity, and their role in lidocaine-induced neurotoxicity needs to be explored. Here, we established a rat model of lidocaine-induced neurotoxicity via the repetitive intrathecal administration of 10% lidocaine. Thereafter, microarray and bioinformatics analyses were performed to evaluate the changes in lncRNA and mRNA expression profiles in the lumbar spinal cord of the treated rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was also employed for verification. The lidocaine-treated rats (group L) showed elevated paw withdrawal threshold (PWT) as well as histopathological injuries in the lumbar spinal cord compared with the control saline-treated rats (group N). Further, relative to group N, microarray analysis showed 179 and 675 differentially expressed lncRNAs (DElncRNAs) and DEmRNAs in the lumbar spinal cord of rats in the group L, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEmRNAs showed that the most significantly enriched functions and pathways were those associated with cell cycle and immuno-inflammatory processes. Furthermore, coding-noncoding co-expression analysis showed multiple lncRNAs that were co-expressed with factors that regulate inflammation. Additionally, by constructing a preliminary competitive endogenous RNA (ceRNA) network analysis, we established a regulatory network of the lncRNAs and mRNAs that are potentially involved in lidocaine-induced neurotoxicity. In conclusion, our findings provide new insights into the molecular mechanisms of lidocaine-induced neurotoxicity; this has significance with respect to the identification of novel therapeutic targets.

Keywords: Bioinformatics analysis; Lidocaine; LncRNA; Neurotoxicity; mRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gene Regulatory Networks
Lidocaine / toxicity
MicroRNAs* / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Messenger / metabolism
Rats
Spinal Cord / metabolism

Substances

MicroRNAs
RNA, Long Noncoding
RNA, Messenger
Lidocaine