Imatinib inhibits oxidative stress response in spinal cord injury rats by activating Nrf2/HO-1 signaling pathway.

Abstract

Effect of imatinib on rats with spinal cord injury (SCI) was investigated through the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Forty-eight Sprague-Dawley rats were randomly divided into sham operation group (n=12), model group (n=12), imatinib group (n=12) and inhibitor group (n=12). The results of immunohistochemistry showed that in comparison with sham operation group, the other three groups had overtly increased positive expression level of Bax and evidently reduced positive expression level of Bcl-2 (P<0.05). Compared with those in model group and inhibitor group, the positive expression level of Bax was distinctly lower, while that of Bcl-2 was notably increased in imatinib group (P<0.05). According to western blot analysis, the protein expression levels of Nrf2 and HO-1 were obviously higher in the other three groups than those in sham operation group (P<0.05), and they were remarkably higher in imatinib group than those in model group and inhibitor group (P<0.05). The results of qPCR assay revealed that the Nrf2 and HO-1 mRNA expression levels were markedly elevated in the other three groups compared with those in sham operation group (P<0.05). Based on ELISA, the other three groups exhibited notably raised content of IL-6, TNF-α, ROS and SOD compared with sham operation group (P<0.05), and imatinib group displayed remarkably decreased content of IL-6, TNF-α and ROS and markedly elevated SOD content in comparison with model group and inhibitor group (P<0.05). The results of TUNEL assay demonstrated that the rate of apoptosis was significantly raised in the other three groups compared with that in sham operation group (P<0.05), and it declined obviously in imatinib group compared with that in model group and inhibitor group (P<0.05). Imatinib inhibits oxidative stress response in SCI rats by activating the Nrf2/HO-1 signaling pathway, thus repressing apoptosis and inflammation.