Role of ERK signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion (I/R) injury in rats. Methods Eighty clean-grade male Sprague-Dawley rats, aged 9-10 weeks, weighing 300-350 g, were divided into 4 groups (n=20 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R), dexmedetomidine group (group D), and dexmedetomidine plus ERK signaling pathway blocker PD98059 group (group P). Spinal cord ischemia was produced by cross-clamping of the abdominal aorta distal to the left renal artery for 25 min followed by reperfusion to establish the model of spinal cord I/R injury.Dexmedetomidine 1 μg/kg was intrathecally injected at 20 min before establishing the model in D and P groups, PD98059 2 mg/kg was given via the tail vein at the same time in group P, and the equal volume of normal saline was given instead in S and I/R groups.Five rats were selected at 6, 8, 10 and 12 h of reperfusion, and the modified Basso, Beattie, Bresnahan (BBB) scale was used to assess the hindlimb locomotor function.Five rats were sacrificed after assessing the locomotor function at 6 h of reperfusion, and the L3-5 segments of the spinal cord were taken for determination of cell apoptosis (by TUNEL) and expression of phosphorylated ERK (p-ERK) (by Western blot). The apoptosis index was calculated. Results Compared with group S, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in the other three groups (P 0.05). Compared with group D, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was down-regulated in group P (P<0.05). Conclusion The mechanism by which intrathecal dexmedetomidine reduces spinal cord I/R injury is related to activating ERK signaling pathway in rats. Key words: Dexmedetomidine; Reperfusion injury; Spinal cord; Extracellular signal-regulated MAP kinases