Intrathecal injection of dexmedetomidine improves neuromotor function in rats with spinal cord ischemia-reperfusion injury based on the CXCR4-FAK signaling pathway
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1.Sports Hospital Affiliated to Chengdu Institute of Physical Education, Chengdu 610000, China. 2. Sichuan Orthopedic Hospital, Chengdu 610000

Clc Number:

R-33

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    Abstract:

    Objective To investigate whether the protective mechanism by which intrathecal injection of dexmedetomidine improves neuromotor function in rats with spinal cord ischemia-reperfusion injury is based on the CXCR4-FAK signaling pathway. Methods Sixty SPF-grade SD male rats aged 10-12 weeks were randomly divided into four groups ( n = 15 per group): the sham group, model group, DHI group, and DPA group. The SCIRI model was constructed in the model, DHI, and DPA groups by opening the thoracic clipped aortic arch for 15 min. In the sham group, the thoracic free aortic arch was only opened, without clamping. After successful establishment of the model, each rat was fed in a single cage with conventional feed and a standard diet. The DHI and DPA groups were injected in the sheath 72 h before ischemia with DHI and Diprotin A, respectively, with a dose of 30 μL at a concentration of 5 μmol / L. The sham and model groups were injected with the same volume of normal saline, with a fixed point injection once daily for 3 consecutive days. On day 4 after modeling, the neuromotor function score, blood-spinal cord barrier structural integrity, water content, ultrastructural changes, apoptosis, oxidative stress response, and the expression levels of CXCR4 and p-FAK were detected using the improved Tarlov scoring method , Evans blue ( EB) staining, wet / dry weight method , electron microscopy, TUNEL staining, DCFH-DA staining kit, and western blot techniques, respectively. Results Compared with the sham group, the neuromotor function score and SOD activity of the model group were significantly decreased. In contrast, the water content of the spinal cord, EB red fluorescence intensity, apoptosis rate, ROS green fluorescence intensity, MDA content, and CXCR4 and pFAK expression levels were significantly increased. Compared with the model group, the neuromotor function score, SOD activity, and CXCR4 and pFAK expression levels in the spinal cord were significantly increased in the DHI and DPA groups. In contrast, the water content of the spinal cord, EB red fluorescence intensity, apoptosis rate, the green fluorescence intensity of ROS, and MDA content were significantly lower, and these differences were statistically significant (P< 0. 05). There were no significant differences between the DHI and DPA groups ( P> 0. 05). Conclusions The protective effect of dexmedetomidine on SCIRI rats may be caused by the activation of the CXCR4-FAK signaling pathway, thus reducing oxidative stress injury in cells, and playing a protective role in the spinal cord of SCIRI rats.

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  • Received:November 12,2019
  • Online: May 14,2020
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