Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver
Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver
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DOI：
10.1007/s00011-005-0060-y
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发表时间：
2006-03-01
影响因子：
6.7
通讯作者：
Li, JS
中科院分区：
文献类型：
--
作者：
Li, G;Qi, XP;Li, JS
目标：探讨维拉帕米对脂多糖（LPS）诱导的细胞因子（肿瘤坏死因子-α）的影响（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）]和核因子κ B方法和材料：成年雄性Sprague-Dawley大鼠随机分为7组，每组8只：对照组用生理盐水处理，（0.9%NaCl）;用盐水处理然后用LPS（10 mg/kg）腹膜内攻击的大鼠;用不同水平的维拉帕米（1、2.5、5、10 mg/kg）腹膜内处理然后用LPS（10 mg/kg）攻击的大鼠;和仅用维拉帕米（10 mg/kg）处理的大鼠。结果：LPS刺激肝组织TNF-α、IL-6、IL-10和NF-κ B的产生，并激活NF-κ B。维拉帕米预处理可减轻急性肝损伤，下调LPS诱导的促炎细胞因子的产生（TNF-α和IL-6），上调抗炎细胞因子（IL-10）的产生，并以剂量依赖性方式抑制肝脏中的NF-κ B活化。维拉帕米可能通过抑制NF-κ B B，下调肝脏中TNF-α和IL-6的产生，上调IL-10，从而减轻急性肝损伤。
Objective: To investigate the effect of verapamil on Lipopolysaccharide (LPS)-induced cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10)] and nuclear factor kappa B (NF-kappa B) in the liver.Methods and Materials: Adult male Sprague-Dawley rats were randomly divided into seven groups of eight rats each: control rats treated with saline (0.9% NaCl); rats treated with saline and then challenged intraperitoneally with LPS (10 mg/kg); rats treated intraperitoneally with different levels of verapamil (1, 2.5, 5, 10 mg/kg) and then challenged with LPS (10 mg/kg); and rats treated only with verapamil (10 mg/kg). TNF-alpha, IL-6, IL-10 and NF-kappa B in the liver tissues were investigated as well as the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) one hour after LPS injection.Results: LPS alone stimulated production of TNF-alpha, IL-6 and IL-10, and activated NF-kappa B in the liver. Pretreatment with verapamil before LPS challenge reduced acute liver injury, down-regulated production of LPS-induced pro-inflammatory cytokines (TNF-alpha and IL-6), up-regulated production of anti-inflammatory cytokines (IL-10) and inhibited NF-kappa B activation in the liver in a dose-dependent manner.Conclusion: Verapamil can attenuate acute liver injury by down-regulating the production of TNF-alpha and IL-6 and up-regulating IL-10 in the liver, possibly via inhibition of NF-kappa B.