title: Simvastatin inhibits ischemia/reperfusion injury-induced apoptosis of retinal cells via downregulation of the tumor necrosis factor-α/nuclear factor-κB pathway.
abstract: 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-α (TNF-α) and nuclear factor-κB (NF-κB) expression in the retina. These findings strongly suggested that simvastatin inhibits apoptosis following IR-induced retinal injury by inhibition of the TNF-α/NF-κB pathway. The present study also provided a rationale for developing therapeutic methods to treat IR-induced retinal injury in the clinic.
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Zhuhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D020011:Protective Agents / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012160:Retina / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D019821:Simvastatin / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D016328:NF-kappa B; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019821:Simvastatin