Suppr超能文献

MK2信号通路在颈脊髓慢性压迫中的作用

Role of MK2 signaling pathway in the chronic compression of cervical spinal cord.

作者信息

Song Hongxing, Fang Xiutong, Wen Mingjie, Yu Fang, Gao Kai, Sun Chenli, Wang Zhenwei

机构信息

Department of Orthopaedics Surgery, Beijing Shijitan Hospital, Capital Medical University, The Ninth Clinical Medical College of Peking University Beijing 100038, China.

Department of Immunology, School of Basic Medical Sciences, Capital Medical University Beijing 100069, China.

出版信息

Am J Transl Res. 2015 Nov 15;7(11):2355-63. eCollection 2015.

Abstract

OBJECTIVE

In this study, chronic compression of cervical spinal cord was introduced into twy/twy mice and the role of MK2 signaling pathway was investigated in this disease.

METHODS

twy/twy mice aged 6-24 weeks were used and the inflammatory response in the cervical spinal cord was observed. The Institute of Cancer Research (ICR) mice were used as controls. MK2 inhibitor (PF-3644022, 30 mg/kg) was administered intragastrically to twy/twy mice. The motor behavior was firstly observed in these three groups by Catwalk gait analysis. And the cervical spinal cord between C2 and C3 of vertebral segments was analyzed by MRI and Western blot assay.

RESULTS

The stride length of paws and interlimb coordination reduced in twy/twy mice. However, at 4 weeks after PF-3644022 treatment, a marked improvement was observed in the motor function. The expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2 and p-MK2) and apoptosis related proteins (such as cleaved caspase-8 and bax/bcl-2) in the spinal cord of twy/twy mice significantly increased as compared to controls, but 4-week treatment with PF-3644022 markedly reduced the expressions of these factors and apoptotic proteins in the cervical spinal cord.

CONCLUSION

MK2 signaling pathway is involved in the chronic compression induced inflammation of the cervical spinal cord. Thus, to inhibit the MK2 pathway may used to improve the outcome and prevent the deterioration of neurological dysfunction.

摘要

目的

在本研究中,将颈脊髓慢性压迫引入twy/twy小鼠,并研究MK2信号通路在该疾病中的作用。

方法

使用6至24周龄的twy/twy小鼠,观察颈脊髓中的炎症反应。以癌症研究所(ICR)小鼠作为对照。对twy/twy小鼠进行灌胃给予MK2抑制剂(PF-3644022,30mg/kg)。首先通过Catwalk步态分析观察这三组小鼠的运动行为。并通过MRI和蛋白质免疫印迹分析对椎骨节段C2和C3之间的颈脊髓进行分析。

结果

twy/twy小鼠的爪步幅长度和四肢间协调性降低。然而,在PF-3644022治疗4周后,观察到运动功能有明显改善。与对照组相比,twy/twy小鼠脊髓中炎症相关因子(如IL-1β、NF-κB、TNF-α、MK2和p-MK2)以及凋亡相关蛋白(如裂解的半胱天冬酶-8和bax/bcl-2)的表达显著增加,但PF-3644022治疗4周显著降低了颈脊髓中这些因子和凋亡蛋白的表达。

结论

MK2信号通路参与了颈脊髓慢性压迫诱导的炎症反应。因此,抑制MK2通路可能用于改善病情并预防神经功能障碍的恶化。

相似文献

1
Role of MK2 signaling pathway in the chronic compression of cervical spinal cord.
Am J Transl Res. 2015 Nov 15;7(11):2355-63. eCollection 2015.
2
Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord.
Ann Palliat Med. 2021 Feb;10(2):1304-1312. doi: 10.21037/apm-20-396. Epub 2020 Sep 24.

引用本文的文献

1
Evidence of impaired macroautophagy in human degenerative cervical myelopathy.
Sci Rep. 2022 Jul 13;12(1):11873. doi: 10.1038/s41598-022-15158-x.
2
Ultrastructural Features of Neurovascular Units in a Rat Model of Chronic Compressive Spinal Cord Injury.
Front Neuroanat. 2018 Jan 10;11:136. doi: 10.3389/fnana.2017.00136. eCollection 2017.

本文引用的文献

1
Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo.
J Integr Med. 2014 Nov;12(6):483-94. doi: 10.1016/s2095-4964(14)60057-1.
2
Mitogen-activated protein kinases in innate immunity.
Nat Rev Immunol. 2013 Sep;13(9):679-92. doi: 10.1038/nri3495. Epub 2013 Aug 19.
3
Inhibition of MK2 shows promise for preventing postoperative ileus in mice.
J Surg Res. 2013 Nov;185(1):102-12. doi: 10.1016/j.jss.2013.05.028. Epub 2013 May 31.
4
17β-estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells.
Mol Cell Biochem. 2013 Jul;379(1-2):201-11. doi: 10.1007/s11010-013-1642-6. Epub 2013 Apr 9.
5
Dynamin-2 mediates heart failure by modulating Ca2+ -dependent cardiomyocyte apoptosis.
Int J Cardiol. 2013 Oct 3;168(3):2109-19. doi: 10.1016/j.ijcard.2013.01.006. Epub 2013 Feb 11.
6
MSK1 and MSK2 inhibit lipopolysaccharide-induced prostaglandin production via an interleukin-10 feedback loop.
Mol Cell Biol. 2013 Apr;33(7):1456-67. doi: 10.1128/MCB.01690-12. Epub 2013 Feb 4.
10
Ossification of the posterior longitudinal ligament of the cervical spine: etiology and natural history.
Spine (Phila Pa 1976). 2012 Mar 1;37(5):E309-14. doi: 10.1097/BRS.0b013e318241ad33.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验