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神经生长因子预处理通过增加 BDNF 表达和抑制大鼠脊髓中 p38 丝裂原活化抑制利多卡因诱导的髓鞘损伤。

Nerve growth factor pretreatment inhibits lidocaine‑induced myelin damage via increasing BDNF expression and inhibiting p38 mitogen activation in the rat spinal cord.

机构信息

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):4678-4684. doi: 10.3892/mmr.2017.7197. Epub 2017 Aug 9.

DOI:10.3892/mmr.2017.7197
PMID:28849178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5647042/
Abstract

The present study aimed to investigate the effect of exogenous nerve growth factor (NGF) pretreatment on demyelination in the spinal cord of lidocaine‑treated rats, and explored the potential neuroprotective mechanisms of NGF. A total of 36 rats were randomly assigned to three groups (n=12 per group): Sham group; Lido group, received intrathecal injection of lidocaine; NGF group, received intrathecal injection of NGF followed by intrathecal injection of lidocaine. Tail‑flick tests were used to evaluate neurobehavioral function. Ultrastructural alternations were analyzed by transmission electron microscopy. Immunofluorescence was used to examine the expression of myelin basic protein (MBP) and brain‑derived neurotrophic factor (BDNF). ELISA was used to determine serum levels of MBP and proteolipid protein (PLP). Western blotting was used to detect the expression of phosphorylated mitogen activated protein kinase (MAPK). NGF pretreatment reduced lidocaine‑induced neurobehavioral damage, nerve fiber demyelination, accompanied by a decrease in MBP expression in the spinal cord and an increase in MBP and PLP in serum. In addition, NGF pretreatment increased BDNF expression in the spinal cord of lidocaine‑treated rats. Furthermore, NGF pretreatment reduced p38 MAPK phosphorylation in the spinal cord of lidocaine‑treated rats. NGF treatment reduces lidocaine‑induced neurotoxicity via the upregulation of BDNF and inhibition of p38 MAPK. NGF therapy may improve the clinical use of lidocaine in intravertebral anesthesia.

摘要

本研究旨在探讨外源性神经生长因子(NGF)预处理对利多卡因处理大鼠脊髓脱髓鞘的影响,并探讨 NGF 的潜在神经保护机制。将 36 只大鼠随机分为三组(每组 n=12):假手术组;利多卡因组,鞘内注射利多卡因;NGF 组,鞘内注射 NGF 后鞘内注射利多卡因。采用甩尾试验评估神经行为功能。采用透射电镜分析超微结构改变。免疫荧光法检测髓鞘碱性蛋白(MBP)和脑源性神经营养因子(BDNF)的表达。ELISA 法测定血清 MBP 和蛋白脂质蛋白(PLP)水平。Western blot 法检测磷酸化丝裂原活化蛋白激酶(MAPK)的表达。NGF 预处理可减轻利多卡因诱导的神经行为损伤和神经纤维脱髓鞘,同时降低脊髓 MBP 表达,增加血清 MBP 和 PLP。此外,NGF 预处理可增加利多卡因处理大鼠脊髓中 BDNF 的表达。此外,NGF 预处理可降低利多卡因处理大鼠脊髓中 p38 MAPK 的磷酸化。NGF 治疗通过上调 BDNF 和抑制 p38 MAPK 减轻利多卡因诱导的神经毒性。NGF 治疗可能改善利多卡因在椎间麻醉中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/24897d6772bb/MMR-16-04-4678-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/77b704620653/MMR-16-04-4678-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/107811e55885/MMR-16-04-4678-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/95587c038013/MMR-16-04-4678-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/389aae3dd470/MMR-16-04-4678-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/24897d6772bb/MMR-16-04-4678-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/77b704620653/MMR-16-04-4678-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/107811e55885/MMR-16-04-4678-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/95587c038013/MMR-16-04-4678-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/389aae3dd470/MMR-16-04-4678-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6942/5647042/24897d6772bb/MMR-16-04-4678-g04.jpg

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