ABSTRACT
Objective To investigate the effect of the peroxide proliferator-activated receptorgamma (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 μ mol/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).At 28 days after operation,the rosiglitazone group had the highest BBB score [(14.7 ± 1.6) points],and the BBB score of rosiglitazone + Clostridium chitosans group (10.5 ± 2.1) points was superior to that of rosiglitazone + monosodium urate group [(7.2 ± 1.3)points,P ＜ 0.05].The expressions of IL-1β and TNF-α in rosiglitazone + monosodium uric acid group were lower than those in other groups at 28 days after injury (P ＜ 0.05).In vitro,the expressions of caspase-1,NF-kappa B,IL-1β and TNF-α in rosiglitazone group were lower than those in negative control group (P ＜ O.05).The expressions of caspase-1,NLRP3,IL-1β and TNF-α in rosiglitazone + Clostridium chitosani group were higher than those in rosiglitazone group,(P ＜ 0.05).The expressions of caspase-1 and IL-1β were higher than those in Clostridium chitosani + MCC950 group (P ＜0.05),but there was no significant difference in the expression of TNF-α between the two groups (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.