Abstract
Objective To investigate the inhibitory effect of peroxisome proliferator activated receptor gamma (PPARγ) agonist on autophagy-associated proteins in rats after spinal cord injuries. Methods A total of 60 rats were randomly divided into the sham operation group, model group, agonist group and inhibitor group, with 15 rats in each group. The spinal cord was exposed by laminectomy and the model of spinal cord injuries was established by an epidural compression of the spinal cord with a sterile artery clip at the T6-T7 segment. Rats in the sham operation group only performed laminectomy. Rats in the agonist and inhibitor groups were intraperitoneally injected with rosiglitazone and GW9662 (2 mg/kg, once every 2 hours) respectively after spinal cord injuries and rats in the sham operation and model groups were given an equal dose of isotonic NaCl solution by intraperitoneal injection. The hindlimb motor function was assessed on 3, 5, 7, 14, 21, and 28 d after spinal cord injuries using the Tarlov's scoring method. The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1 and cathepsin D were detected by Western-blotting and the PPARγ mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). Results The Tarlov's scores at different time points among 4 groups were significantly different (F = 25.674, P < 0.001). Compared with the sham operation group, the Tarlov's scores in the other 3 groups decreased obviously on 3, 5, 7, 14, 21, and 28 d after spinal cord injuries (all P < 0.05); the Tarlov's scores in the agonist group were much higher than those in the model and inhibitor groups (all P < 0.05). The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1, cathepsin D and PPARγ mRNA on 3 d after spinal cord injuries were significantly different among 4 groups as well (F = 238.213, 28.268, 172.563, 32.492; all P < 0.001). The expressions of LC3-Ⅱ/LC3-Ⅰ, beclin-1, cathepsin D and PPARγ mRNA in the sham operation group were much lower than those in the other 3 groups (all P < 0.05). Compared with the agonist group, the expressions of LC3-Ⅱ/LC3-Ⅰ and PPARγ mRNA decreased, and the expressions of beclin-1 and cathepsin D increased in the model and inhibitor groups (all P < 0.05). Conclusion The PPARγ agonist can promote the recovery of neurological function in rats after spinal cord injuries by down-regulating the expressions of autophagy-associated proteins. Key words: PPAR gamma; Spinal cord injuries; Autophagy; Rats
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