Song Hongxing, Fang Xiutong, Wen Mingjie, Yu Fang, Gao Kai, Sun Chenli, Wang Zhenwei
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.
Am J Transl Res. 2015 Nov 15;7(11):2355-63. eCollection 2015.
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.
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.
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.
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.
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。
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。
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。
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。