Simvastatin inhibits ischemia/reperfusion injury-induced apoptosis of retinal cells via downregulation of the tumor necrosis factor-alpha/nuclear factor-kappa B pathway

摘要

Simvastatin, which is widely used in the prevention and treatment of hyperlipidemia-associated diseases, has been reported to enhance the survival of retinal ganglion cells (RGCs) in a model of retinal ischemia/reperfusion (IR) injury. However, the underlying mechanism of the anti-apoptotic effects of simvastatin on the retina have yet to be elucidated. In the present study, rats were treated with simvastatin or saline for 7 days prior to IR via ligation of the right cephalic artery. The results showed that simvastatin prevented the apoptosis of RGCs and cells in the inner nuclear layer. Furthermore, simvastatin regulated the expression of apoptosis-associated proteins. The expression levels of the anti-apoptotic protein B-cell lymphoma-2 were upregulated 4 and 24 h after IR in the simvastatin/IR group compared to those in the saline/IR group. Conversely, the levels of pro-apoptotic protein Bax were downregulated in the simvastatin/IR group compared to those in the saline/IR group. Furthermore, the results of the present study showed for the first time, to the best of our knowledge, that simvastatin decreased IR injury-induced tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappa B (NF-kappa B) expression in the retina. These findings strongly suggested that simvastatin inhibits apoptosis following IR-induced retinal injury by inhibition of the TNF-alpha/NF-kappa B pathway. The present study also provided a rationale for developing therapeutic methods to treat IR-induced retinal injury in the clinic.