Neuroprotective effect of tamoxifen in a model rat with aucte spinal cord injury
10.3969/j.issn.2095-4344.2016.51.017
- VernacularTitle:他莫昔芬对急性脊髓损伤模型大鼠的神经保护
- Author:
Wei HUANG
- From:
Chinese Journal of Tissue Engineering Research
2016;20(51):7710-7716
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:Tamoxifen has been found to exert neuroprotection by reducing cerebral hemorrhage and edema surrounding the injured site of the spinal cord.
OBJECTIVE:To investigate the neuroprotective effect of tamoxifen on rat acute spinal cord injury and the underlying mechanism.
METHODS:Sixty Sprague-Dawley rats were equivalently randomized into five groups, and modeled into spinal cord injury at T10 level using modified Al en’s weight-drop method (70 g/cm), except those in sham operation group. At 30 minutes after modeling, al rats were given the intraperitoneal injection of 2.5, 5.0 and 10 mg/kg tamoxifen or same amount of normal saline, once daily. Basso, Beattie, Bresnahan (BBB) scores were recorded at 24, 48 and 72 hours after surgery. The injured spinal cord was removed at 72 hours to observe its edema. Meanwhile, the levels of interleukin-1β, interleukin-10 and tumor necrosis factor-α, as wel as Caspase-3 activity were detected by ELISA;the protein levels of nuclear factor-κB p65, phosphorylated I-κBαand Caspase-3 were detected by western blot assay.
RESULTS AND CONCLUSION:Compared with the model group, the hind limb function in the tamoxifen groups was significantly improved. Tamoxifen significantly decreased the water content in the rat spinal cord and inhibited spinal cord edema at 72 hours after surgery. ELISA results showed that tamoxifen significantly reduced the activity of interleukin-1β, interleukin-10, tumor necrosis factor-αand Caspase-3 (P<0.05). Western blot assay revealed that tamoxifen significantly downregulated the expression levels of nuclear factor-κB p65, phosphorylated I-κBαand Caspase-3. These results suggest that tamoxifen protects against spinal cord injury via suppressing inflammatory response and apoptosis-associated proteins.