Amlodipine and atorvastatin improve ventricular hypertrophy and diastolic function via inhibiting TNF-α, IL-1β and NF-κB inflammatory cytokine networks in elderly spontaneously hypertensive rats

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• 作者：Jingchao Lu ; Fan Liu ; Fei Chen ; Yaqiong Jin ; Huiqiang Chen ; Demin Liu ; Wei Cui ; ^{cuiwei21c@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TNF-α ; tumor necrosis factor-alpha ; IL-1β ; Interleukin-1β ; Hs-CRP ; high sensitive C reactive protein ; NF-κb ; nuclear factor-kappa B ; IκB ; inhibitor-kappa B ; MMP ; matrix metalloproteinase ; DEPC ; diethypyocarbonate
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：330-339
• 全文大小：3055 K

文摘

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-α and IL-1β levels were assessed by radioimmunity assay (RIA). Cardiac inflammatory cell infiltration was observed by HE staining. The protein levels of TNF-α, IL-1β, of NF-κB P65 and IκBα were detected by immunoblotting. The intracellular localization of NF-κB 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-1β 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-1β level in SH rats. Moreover, amlodipine or atorvastatin intervention significantly reduced myocardial TNF-α and IL-1β 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-κB signaling in SH rats, which was further suppressed by combinatorial treatment. Furthermore, amlodipine or atorvastatin restored the activity of IκB-α 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-α, IL-1β, NF-κB/IκB inflammatory cytokine network. Our study suggests that amlodipine combined with atorvastatin may have additive effect on inhibiting inflammatory response.