Effect of rosiglitazone on motor function recovery of hind limbs in rats with spinal cord injury

Abstract

Objective To investigate the effect of the peroxide proliferator-activated receptor-gamma (PPAR-γ) agonist rosiglitazone on the motor function recovery of hind limbs in rats with spinal cord injury. Methods Sixty-eight female SD rats were used to establish spinal cord injury model by modified Allen method. (1) Eight rats were randomly divided into negative control group and rosiglitazone group with four rats in each group. The expression of aspartate proteolytic enzyme-1 (caspase-1) in spinal cord of rats 7 days after injury was detected by immunohistochemical staining. (2) Forty-eight rats were randomly divided into negative control group, rosiglitazone group, rosiglitazone+ Clostridium chitosans group [nuclear factor kappa B (NF-kappa B) activator], rosiglitazone+ monosodium urate group [oligomerization domain-like receptor protein 3 (NLRP3) antagonist], with 12 rats in each group. BBB scores of hindlimb motor function were assessed at 1, 3, 14, 21 and 28 days after injury in each group. The expression of interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in each group was detected by ELISA at 28 days after injury. Microglia were isolated from the spinal cord of 12 rats and cultured for 7 days. They were randomly divided into the following five groups: (1) negative control group: no drug treatment; (2) rosiglitazone group: 1 micromol/L rosiglitazone treatment; (3) rosiglitazone+ Clostridium chitin group: 1 micromol/L rosiglitazone+ 20 micromol/L Clostridium chitosporin treatment; (4) Clostridium chitosan treatment Mycoplasma group: 20 μmol/L shell Clostridium treatment; (5) Clostridium chitosanin+ MCC950 group [(NLRP3) antagonist]: 20 μmol/L Clostridium chitosanin+ 100 nmol/L MCC950; Western blot was used to detect the expressions of caspase-1, NF-kappa B and NLRP3 in microglia cells; ELISA was used to detect the expressions of IL-1β and TNF-α in the supernatant of microglia culture. Results Compared with negative control group, caspase-1 expression was decreased in rosiglitazone group in spinal cord injury area [gray matter area: 5.1±0.8∶6.9±1.1; white matter area: 5.6±0.9∶7.5±1.1](P 0.05). Conclusion Rosiglitazone can promote the recovery of hind limb motor function in rats with spinal cord injury by inhibiting the expression of NF-kappa B, thereby reducing the activation of NLRP3 inflammatory bodies in microglia and ultimately inhibiting the occurrence of inflammation. Key words: Spinal cord injuries; Rosiglitazone; Microglia; Rats