Neuroprotective effects of curcumin on spinal cord injury mice by nuclear factor E2-related factor 2 pathway

Abstract

Objective To investigate the neuroprotective effect of curcumin (CCM) on spinal cord injury (SCI) mice by nuclear factor related factor 2 (Nrf2)/ARE pathway. Methods The SCI mouse model was prepared by modified Allen’s hitting method. At 3 days after SCI, the number of necrotic cells near the injured area was detected by propidium iodide (PI) staining. Hydroethidine (HEt) staining was used to detect reactive oxygen species (ROS) production. enzyme linked immunosorbent assay (ELISA) kit was used to detect the expression of tumor necrosis factor-α (TNF-α) and interleukin- 10 (IL- 10). At 28 days after SCI, Basso Mouse Scale (BMS) score was used to detect the hindlimb motor function. Sucorse preference test was used to evaluate the depressive status of mice. The expression of Nrf2, SOD1 and quinone oxidoreductase gene (NQO1) were detected by Western blotting. Results (1) The spinal cord water content (75.540±1.564) in the CCM group was significantly lower than that in the Veh group (85.500±1.297), the difference was statistically significant (t=4.903, P=0.001). (2) BMS scores showed that CCM treatment group 7, 14, 21 and 28 d scores of hindlimb locomotor function [(2.400±0.894), (3.400±0.894), (4.200±0.837) and (4.800±0.837) scores] compared with the Veh Group [(1.000±0.707), (1.800±0.447), (2.200±0.837), (3.000±0.707) scores, P= 0.004]. (3) Sucorse preference test showed that the difference between the CMM treatment group and the Veh group was statistically significant [(55.330±1.124)% and (45.740±1.965)%, t=4.314, P=0.002]. (4) Compared with Veh group, CCM group of anti- inflammatory cytokines IL- 10 expression (674.20±6.94) was significantly higher than that of group Veh (525.00±6.43), and proinflammatory factor TNF- α (763.20±16.24) was significantly lower than that of Veh group (1 091.00±29.02), P=0.000, 0.000. (5) The fluorescence intensity of ROS in CCM group (1 377.00±27.06) was significantly lower than Veh group (1 750.00±42.45), the difference was statistically significant (t=7.410, P=0.000). (6) Compared with Veh group (72.00±3.81), the number of necrotic cells in CCM group was significantly decreased (53.60±3.20), and the difference was statistically significant (t=3.690, P=0.006). (7) Compared with Veh group, the expression of SOD1、Nrf2 and NQO1 in CCM group were up- regulated (0.763±0.039, 0.442±0.026, 0.636±0.023 and 0.937±0.030, 0.692±0.034, 0.898±0.025, P=0.025, 0.004, 0.002). Conclusion Curcumin protects neurons in spinal cord injury by Nrf2 pathway. Key words: Curcumin; Spinal cord injury; Nuclear factor related factor 2 pathway; Neuroprotection