Li G, Qi X P, Wu X Y, Liu F K, Xu Z, Chen C, Yang X D, Sun Z, Li J S
School of Medicine, Nanjing University, Department of General Surgery, Jinling Hospital, 305 Zhongshangdong Road, Nanjing, 210002, Jingsu Province, China.
Inflamm Res. 2006 Mar;55(3):108-13. doi: 10.1007/s00011-005-0060-y.
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.
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.
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.
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.
研究维拉帕米对脂多糖（LPS）诱导的肝脏细胞因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）]及核因子κB（NF-κB）的影响。
成年雄性Sprague-Dawley大鼠随机分为7组，每组8只：用生理盐水（0.9% NaCl）处理的对照大鼠；先用生理盐水处理，然后腹腔注射LPS（10 mg/kg）的大鼠；腹腔注射不同剂量维拉帕米（1、2.5、5、10 mg/kg），然后注射LPS（10 mg/kg）的大鼠；仅用维拉帕米（10 mg/kg）处理的大鼠。在注射LPS 1小时后，检测肝脏组织中的TNF-α、IL-6、IL-10和NF-κB，以及血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平。
单独使用LPS刺激肝脏中TNF-α、IL-6和IL-10的产生，并激活NF-κB。在LPS攻击前用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（TNF-α和IL-6）的产生，上调抗炎细胞因子（IL-10）的产生，并以剂量依赖方式抑制肝脏中NF-κB的激活。
维拉帕米可能通过抑制NF-κB，下调肝脏中TNF-α和IL-6的产生，上调IL-10的产生，从而减轻急性肝损伤。
