Abstract: BACKGROUND: Spinal cord ischemia-reperfusion injury is commonly seen in surgical treatments during extracorporeal circulation. Once it occurs, the consequences are serious. Therefore, it is of great significance to avoid the occurrence of spinal cord ischemia-reperfusion injury. Tetrandrine seems to protect spinal cord ischemia-reperfusion injury through multiple approaches.
OBJECTIVE: To study the protective effect and mechanism of tetrandrine preconditioning on spinal cord ischemia-reperfusion injury in rabbits.
METHODS: Forty-eight New Zealand rabbits were randomly divided into three groups (n=16 per group). Rabbit spinal cord ischemia-reperfusion model was made by using abdominal aorta occlusion. The sham operation group only exposed the abdominal aorta, but did not clamp the abdominal aorta while the abdominal aorta was clamped in the ischemia-reperfusion group for 30 minutes. Tetrandrine (22.5 mg/kg) was injected through the ear vein of the rabbit at 1 hour before operation in the tetrandrine pretreatment group. The abdominal aorta was then clamped for 30 minutes after opening the abdominal cavity, and then the rabbits were perfused for 48 hours. The motor function of hind limbs was evaluated by Tarlov scores at 24 hours and 48 hours after spinal cord ischemia-reperfusion injury in rabbits. The rabbits in each group were sacrificed after deep anesthesia and the lumbar spinal cord was taken out. Hematoxylin-eosin staining was used to observe the necrosis of spinal nerve cells in rabbits. Evans blue was used to observe the permeability of blood-spinal barrier; enzyme linked immunosorbent assay (ELISA) was used to test the expression of tumor necrosis factor-α; and mitochondrial permeability transition pore kit was adopted to measure the changes in fluorescence intensity to reflect the open changes of mitochondrial permeability transition pore.
RESULTS AND CONCLUSION: Motor function scores of hind limbs: Compared with the sham operation group, the Tarlov scores were significantly lower in the ischemia-reperfusion group and tetrandrine pretreatment group at 24 hours and 48 hours after operation (P < 0.05), and the Tarlov scores in the ischemia-reperfusion group were lower than those in the tetrandrine pretreatment group at 24 hours and 48 hours after operation (P < 0.05). Hematoxylin-eosin staining indicated that: the cell morphology was normal in the sham operation group; the necrotic nerve cells were noted in the other two groups, but tetrandrine pretreatment group was superior to the ischemia-reperfusion group. The permeability of Evans blue decreased significantly in the sham operation group compared with the other two groups (P < 0.05). Moreover, the permeability of Evans blue in the ischemia-reperfusion group was significantly higher than that in the tetrandrine pretreatment group (P < 0.05). Tumor necrosis factor-α level in the spinal cord was extremely lower in the sham operation group than the other two groups (P < 0.05). Compared with the tetrandrine pretreatment group, the level of tumor necrosis factor-α in the spinal cord was significantly increased in the ischemia-reperfusion group (P < 0.05). The fluorescence intensity of mitochondrial permeability transition pore was stronger in the sham operation group than the other two groups (P < 0.05), and lower in the ischemia-reperfusion group than the tetrandrine pretreatment group (P < 0.05). To conclude, tetrandrine preconditioning has a protective effect on spinal cord ischemia-reperfusion injury in rabbits, and its mechanism may be associated with protecting blood-spinal cord barrier, inhibiting the expression of tumor necrosis factor-α and inhibiting the opening of mitochondrial permeability transition pore.

Key words: tetrandrine, spinal cord, ischemia-reperfusion injury, mitochondrial permeability transition pore, neurological function