罗哌卡因通过抑制 MAPK/ NF-κB 通路减轻大鼠脑缺血再灌注损伤

doi:10.3870/j.issn.1672-8009.2023.03.004

摘要/Abstract

摘要： 目的研究罗哌卡因对脑缺血再灌注 (CI/ R) 大鼠脑损伤和海马神经元凋亡的缓解作用及其相关通路。方法 Sprague-Dawley (SD) 大鼠分组: 对照组, CI/ R 模型组, 罗哌卡因治疗组 [低浓度 (0. 5 mg / kg)、中浓度 (1 mg / kg)、高浓度 (2 mg / kg)]。跳台实验和 Y 迷宫实验评价各组大鼠行为学; Longa 法评价大鼠神经功能损伤; HE 染色观察脑组织病理损伤; TUNEL 染色检测海马区组织凋亡; Western 印迹检测相关蛋白的表达。结果与对照组比较, CI/ R 组大鼠跳台试验犯错次数显著增加, 新异臂进入次数显著降低, 脑指数和神经功能缺损评分显著升高; 脑组织出现明显的病理损伤, 海马区神经元明显凋亡; BDNF 和 NGF 蛋白表达显著降低, Bax / Bcl-2 和 cleaved Caspase-3 / Caspase-3 比值显著升高, P38MAPK 和 NF-κB P65 磷酸化水平显著提升。与 CI/ R 组比较, 罗哌卡因治疗改善了 CI/ R 损伤引起的行为学偏差; 显著降低脑指数和神经功能缺损评分; 缓解脑组织损伤和海马体神经元凋亡; 抑制了 P38MAPK/ NF-κB P65 通路的活化。结论罗哌卡因治疗可缓解 CI/ R 大鼠脑损伤和海马神经元凋亡, 其潜在机制或与抑制 MAPK 通路的活化有关。

关键词: 罗哌卡因, 脑缺血再灌注损伤, BDNF, Y 迷宫实验, 凋亡

Abstract: Objective To study the protective effect of ropivacaine on cerebral ischemia / reperfusion (CI/ R) rat brain injury and hippocampal neuronal apoptosis and its mechanism. Methods Sprague-Dawley (SD) rats were divided into 5 groups: control group, CI/ R model group, ropivacaine-low ( 0. 5 mg / kg) group, ropivacaine-medium ( 1 mg / kg) group, and ropivacaine-high (2 mg / kg) group. Step-down test and Y maze test were used to evaluate the behavior of rats in each group. Longa method was used to evaluate the neurological damage in rats. HE staining was used to observe the pathological damage in brain tissue. TUNEL staining was used to detect the apoptosis in hippocampal tissue. Western blotting was used to detect the expression of associated proteins. Results Compared with the control group, the number of errors in step-down test was significantly increased in the CI/ R group, the number of new arm entry were significantly decreased, and the brain index and neurological deficit score were significantly increased. The brain tissue showed obvious pathological damage, and apoptosis was observed in neurons in the hippocampus. The expression levels of BDNF and NGF proteins were significantly decreased, Bax / Bcl-2 and cleaved Caspase-3 / Caspase-3 ratios were significantly increased, and the phosphorylation levels of P38MAPK and NF-κB P65 were significantly increased. Compared with the CI/ R group, ropivacaine treatment improved the behavioral biases caused by CI/ R injury, significantly reduced the brain index and the neurological deficit score. Ropivacaine alleviated brain tissue injury and hippocampus neuron apoptosis. Ropivacaine suppressed the activation of P38MAPK/ NF-κB P65 pathway. Conclusion Ropivacaine treatment can alleviate brain injury and hippocampal neuronal apoptosis in CI/ R rats, and its underlying mechanism may be related to the inhibition of the activation of the MAPK pathway.

Key words: ropivacaine, cerebral ischemia-reperfusion injury, BDNF, Y maze experiment; apoptosis

中图分类号:

R743. 3

石磊, 史静, 刘祥, 张琦, 赵海涛, 李浩. 罗哌卡因通过抑制 MAPK/ NF-κB 通路减轻大鼠脑缺血再灌注损伤 [J]. 医学分子生物学杂志, 2023, 20(3): 209-214.

SHI Lei, SHI Jing, LIU Xiang, ZHANG Qi, ZHAO Haitao, LI Hao. Ropivacaine Alleviates Cerebral Ischemia-reperfusion Injury in Rats by Inhibiting MAPK / NF-κB Pathway [J]. Journal of Medical Molecular Biology, 2023, 20(3): 209-214.

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罗哌卡因通过抑制 MAPK/ NF-κB 通路减轻大鼠脑缺血再灌注损伤

Ropivacaine Alleviates Cerebral Ischemia-reperfusion Injury in Rats by Inhibiting MAPK / NF-κB Pathway

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