摘要

This study aimed to examine the effects of amlodipine and atorvastatin alone or in combination on the regulation of inflammatory cytokines and the underlying mechanisms in elderly spontaneously hypertensive (SH) rats. The level of serum hs-CRP was detected with ELISA. The serum TNF-alpha and IL-1 beta levels were assessed by radioimmunity assay (RIA). Cardiac inflammatory cell infiltration was observed by HE staining. The protein levels of TNF-alpha, IL-1 beta, of NF-kappa B P65 and I kappa B alpha were detected by immunoblotting. The intracellular localization of NF-kappa B p65 was observed using immunohistochemistry. Amlodipine or atorvastatin obviously ameliorated the myocardial inflammatory cell infiltration in SH rats, which was further improved by combinatorial treatment with amlodipine and atorvastatin. Either amlodipine or atorvastatin decreased plasma IL-1 beta content in SH rats, but there was no significant difference when compared with untreated SH rats. However, the combination of amlodipine and atorvastatin significantly decreased plasma IL-1 beta level in SH rats. Moreover, amlodipine or atorvastatin intervention significantly reduced myocardial TNF-alpha and IL-1 beta protein levels in SH rats, which was further suppressed by the combination of amlodipine and atorvastatin. In addition, amlodipine or atorvastatin inhibited the activity of NF-kappa B signaling in SH rats, which was further suppressed by combinatorial treatment. Furthermore, amlodipine or atorvastatin restored the activity of I kappa B-alpha in SH rats, which was enhanced by combinatorial treatment. Our results demonstrated amlodipine and atorvastatin improved ventricular hypertrophy and diastolic function possibly through the intervention of TNF-alpha, IL-1 beta, NF-kappa B/I kappa B inflammatory cytokine network. Our study suggests that amlodipine combined with atorvastatin may have additive effect on inhibiting inflammatory response.