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艾灸通过脊髓中的丝裂原活化蛋白激酶信号通路减轻大鼠慢性炎性内脏痛。

Moxibustion Eases Chronic Inflammatory Visceral Pain In Rats Via MAPK Signaling Pathway In The Spinal Cord.

作者信息

Huang Yan, Zhang Dan, Li Zhi-Yuan, Yang Yan-Ting, Wu Li-Jie, Zhang Ji, Zhi Fang-Yuan, Li Xi-Ying, Shi Zheng, Hong Jue, Ma Xiao-Peng

机构信息

Yueyang Clinical Medical School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.

Acupuncture and Moxibustion Department, Huangpu District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200010, People's Republic of China.

出版信息

J Pain Res. 2019 Nov 7;12:2999-3012. doi: 10.2147/JPR.S218588. eCollection 2019.

Abstract

PURPOSE

The purpose of this study was to explore the central analgesia mechanism of moxibustion for chronic inflammatory visceral pain (CIVP).

METHODS

A CIVP rat model was established by 2,4,6-trinitrobenzene sulfonic acid (TNBS) plus 50% ethanol via enema. The analgesic effect of moxibustion was evaluated using the abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The expression profile of phosphorylated proteins of the mitogen-activated protein kinase (MAPK) signaling pathway in the spinal cord was assayed by protein microarray. The differentially expressed proteins were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional clusters and corresponding signaling pathways.

RESULTS

Moxibustion exerted a significant analgesic effect for CIVP rats, mainly presenting as a decrease in the AWR score (all P<0.01) under different levels of distending pressure and an increase in MWT and TWL thresholds (all P<0.05). Compared with the normal group, 76 proteins were upregulated while 15 were downregulated, and MAPK signaling pathway was activated in the model group. Compared with the model group, there were 53 downregulated and 38 upregulated proteins in the moxibustion group, and MAPK signaling pathway was inhibited. Fold change (FC)>1.3 or <0.77 was taken as the screening standard to define the differentially expressed proteins. Fifteen differentially expressed proteins upregulated in the model group were downregulated in the moxibustion group. GO analysis showed that the differentially expressed proteins mainly controlled cellular metabolism regulation, transportation, and stress reactions. KEGG analysis revealed that these differentially expressed proteins were mostly involved in the ERK, JNK, and p38 pathways, and the ERK pathway was predominant.

CONCLUSION

Moxibustion mitigates CIVP in rats and inhibits the phosphorylation of proteins in the spinal MAPK signaling pathway. The analgesic effect of moxibustion may be associated with the regulation of the spinal MAPK signaling pathway.

摘要

目的

本研究旨在探讨艾灸对慢性炎症性内脏痛(CIVP)的中枢镇痛机制。

方法

采用2,4,6-三硝基苯磺酸(TNBS)加50%乙醇灌肠建立CIVP大鼠模型。通过腹部退缩反射(AWR)、机械性退缩阈值(MWT)和热退缩潜伏期(TWL)评估艾灸的镇痛效果。采用蛋白质芯片检测脊髓中丝裂原活化蛋白激酶(MAPK)信号通路磷酸化蛋白的表达谱。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)对差异表达蛋白进行功能聚类和相应信号通路分析。

结果

艾灸对CIVP大鼠具有显著的镇痛作用,主要表现为在不同程度扩张压力下AWR评分降低(均P<0.01),MWT和TWL阈值升高(均P<0.05)。与正常组相比,模型组有76种蛋白上调,15种蛋白下调,MAPK信号通路被激活。与模型组相比,艾灸组有53种蛋白下调,38种蛋白上调,MAPK信号通路被抑制。以变化倍数(FC)>1.3或<0.77作为筛选标准来定义差异表达蛋白。模型组上调的15种差异表达蛋白在艾灸组中下调。GO分析表明,差异表达蛋白主要控制细胞代谢调节、转运和应激反应。KEGG分析显示,这些差异表达蛋白大多参与ERK、JNK和p38通路,且ERK通路占主导。

结论

艾灸可减轻大鼠CIVP,并抑制脊髓MAPK信号通路蛋白的磷酸化。艾灸的镇痛作用可能与脊髓MAPK信号通路的调节有关。

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