Figure 5
Role of PPAR-α in simvastatin-induced inhibition on iNOS expression and on nitrotyrosine formation. Spinal cord from sham PPAR-αWT mice did not stain for iNOS (panel A a, d and g). Spinal cord sections from injured-PPAR-α WT and from injured-PPAR-α mice (panel A e, g) exhibited positive staining for iNOS (panel A b, g); section from simvastatin-treated PPAR-αWT SCI mice did not reveal any positive staining for iNOS (panel A c, g). The genetic absence of the PPAR-α significantly blocked the effect of the simvastatin on iNOS expression (panel A f, g). In addition, immunohistochemical analysis for nitrotyrosine show positive staining localized in the inflammatory cells in the injured area from SCI-PPAR-αWT mice (panel B b, g). The intensity of the positive staining for nitrotyrosine was markedly increased in tissue section obtained from injured-PPAR-αKO mice (panel B e, g). No positive staining for nitrotyrosine was observed in tissue section from simvastatin-treated PPAR-αWT mice (panel B c, g). The genetic absence of the PPAR-α significantly blocked the effect of simvastatin treatment (panel B f, g). Densitometry analysis of immunocytochemistry photographs (n = 5 photos from each sample collected from all mice in each experimental group) for iNOS (panel A, g) and nitrotyrosine (panel B, g) was assessed. The assay was carried out by using Imaging Densitometer (AxioVision, Zeiss, Milan, Italy). Data are expressed as % of total tissue area. This figure is representative of at least 3 experiments performed on different experimental days. *P < 0.01 vs. Sham; °P < 0.01 vs. SCI-WT group; °°P < 0.01 vs. simvastatin-treated WT group. ND: not detectable.