关键词: 脑源性神经营养因子, 腰椎管狭窄症, 神经元活性, 疼痛, HIF-1α/VEGF, 大鼠

Abstract: BACKGROUND: Studies have found that brain-derived neurotrophic factor deficiency can cause neurodegenerative changes in central motor structures, leading to a variety of motor neurological diseases. Considering lumbar spinal stenosis is a chronic progressive neurological dysfunction syndrome, brain-derived neurotrophic factor may be an effective target for the treatment of this disease.
OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor on neuronal activity, pain and hypoxia-inducible factor-1α/vascular endothelial growth factor in rats with lumbar spinal stenosis. 
METHODS: Forty SPF male Sprague-Dawley rats were randomly divided into normal group, model group, nerve growth factor group, brain derived neurotrophic factor group (n=10 per group). In the latter three groups, animal models of lumbar spinal stenosis were established. After modeling, the rats in the nerve growth factor group was intraperitoneally injected with 1 500 U of nerve growth factor, and those in the brain-derived neurotrophic factor group was intrathecally injected with 20 μL of 10 mg/L brain-derived neurotrophic factor, once a day, for 30 continuous days. The normal and model groups were intragastrically given the same volume of normal saline at the same time. After administration, the motor function and body surface pain of the rats were observed and recorded. Spinal canal density was detected by CT, nerve conduction velocity was measured by nerve trunk action point conduction velocity tester, the neuronal activity of spinal cord tissue was detected by TUNEL method, and the protein expression of hypoxia-inducible factor 1α/vascular endothelial growth factor was detected by western blot.
RESULTS AND CONCLUSION: Compared with the normal group, rats in the model group showed a significant decline in plate movement distance, body surface pain value, and nerve conduction velocity (P < 0.05). Compared with the model group, the above-mentioned indexes were significantly increased in the nerve growth factor group and brain-derived neurotrophic factor group (P < 0.05). Moreover, these indexes were significantly higher in the brain-derived neurotrophic factor group than the nerve growth factor group (P < 0.05). Compared with the normal group, the density of lumbar spinal canals and the apoptotic rate of neurons in spinal cord tissue were significantly increased in the model group (P < 0.05), while the two indexes were significantly decreased after treatment with nerve growth factor and brain-derived neurotrophic factor (P < 0.05). Moreover, the brain-derived neurotrophic factor group showed better effects than the nerve growth factor group (P < 0.05). Compared with the normal group, the model group had significantly increased expression of hypoxia-inducible factor 1α protein and decreased vascular endothelial growth factor in the spinal cord tissue (P < 0.05). Compared with the model group, the protein expression of hypoxia-inducible factor 1α was significantly decreased (P < 0.05) and the expression of vascular endothelial growth factor was significantly increased in the nerve growth factor and brain-derived neurotrophic factor groups (P < 0.05). And the above-mentioned indexes changed significantly in the brain-derived neurotrophic factor group compared with the nerve growth factor group (P < 0.05). To conclude, brain-derived neurotrophic factor has a significant therapeutic effect on lumbar spinal stenosis in the rat model, which can effectively improve neuronal activity, reduce pain, inhibit hypoxia-inducible factor 1α expression, and promote vascular endothelial growth factor expression.

Key words: brain-derived neurotrophic factor, lumbar spinal stenosis, neuronal activity, pain, HIF-1α/VEGF, rat