关键词: 七氟醚, 丙泊酚, 脊髓骨折, 大鼠, 疼痛递质, 神经细胞活性, MAPK/CREB

Abstract: BACKGROUND: Both sevoflurane and propofol have analgesic effects and exert neuroprotective effects by inhibiting neuronal apoptosis, but the specific mechanisms are not fully understood.
OBJECTIVE: To study the effects of sevoflurane combined with propofol on pain mediators, nerve cell activity and mitogen activated protein kinase (MAPK)/cAMP response element binding peotein (CREB) in rats with spinal cord fracture. 
METHODS: Of 80 SPF male Sprague-Dawley rats, 15 rats were randomly selected as healthy group and the remaining rats were used to make animal models of spinal cord fracture. During the modeling, five rats were dead unexpectedly. After successful modeling, 60 model rats were randomized into model group, sevoflurane group, propofol group, and combined group (sevoflurane+propofol), with 15 rats in each group. The rats in the sevoflurane group were placed in a closed experimental box, given an oxygen flow of 2 L/min, and inhaled 2% sevoflurane for 0.5 hours; the rats in the propofol group were injected with 2 mL/kg/h propofol through the tail vein for 4 hours; the rats in the combined group were given both propofol and sevoflurane interventions; and the rats in the healthy group and model group inhaled pure oxygen for 0.5 hours. Von Frey filament method was used to measure mechanical withdrawal threshold values. Hematoxylin-eosin staining was used to observe the pathological morphology of spinal cord tissue of rats. TUNEL was used to detect the apoptosis of neurons in spinal cord tissue of rats. Real-time PCR was used to detect the expression of p38MAPK and CREB mRNA. Western blot assay was used to detect the expression of p38MAPK, CREB, p-p38MAPK, and p75NTR proteins in spinal cord tissue of rats.
RESULTS AND CONCLUSION: (1) Compared with the healthy group, the mechanical withdrawal threshold value was decreased in the other four groups at different time points (P < 0.05). Compared with the model group, the mechanical withdrawal threshold value was significantly increased in the sevoflurane, propofol, and combined groups at different time points (P < 0.05), especially in the combined group (P < 0.05). (2) In the model group, the white matter and central gray matter fused into a large cavity, and the white matter had a large number of vacuoles. In the sevoflurane and propofol groups, there were many cracks in the white matter and central gray matter and massive small vacuoles in the white matter. In the combined group, there were a few cracks in the white matter and central gray matter and a few vacuoles in the white matter. (3) The apoptosis rate of neurons in the model group was significantly higher than that in the sevoflurane, propofol, and combined groups (P < 0.05). The apoptosis rate of neurons was lowest in the combined group (P < 0.05). (4) Compared with the healthy group, the mRNA and protein levels of p38MAPK and CREB were significantly increased in the other four groups (P < 0.05), while the expression of p75NTR was significantly decreased (P < 0.05). Compared with the model group, the expression of p38MAPK mRNA and protein as well as the expression of p-p38MAPK protein decreased in the sevoflurane, propofol, and combined groups, while the expression of CREB mRNA and protein and the expression of p75NTR protein increased (P < 0.05). Changes in the expression of above mRNAs and proteins were most significant in the combined group (P < 0.05). (5) To conclude, sevoflurane combined with propofol can effectively improve neuropathic pain and inhibit neuronal apoptosis in rats with spinal cord fracture, which may be related to inhibiting the expression of p38MAPK and promoting the expression of CREB.

Key words: sevoflurane, propofol, spinal cord fracture, rat, pain mediator, neuronal activity, MAPK/CREB