钙通道阻滞剂对炎症因子平衡的影响及肝保护作用  

Effect of the calcium channel blocker in the balance of LPS-induced inflammatory cytokines expression and its protection of the liver

作　　者：李刚[1] 祁晓平[1] 许哲[1] 陈彻[1] 杨小冬[1] 吴晓宇[1] 孙正[1] 黎介寿[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)解放军普通外科研究所,江苏南京210002

出　　处：《肠外与肠内营养》2005年第6期325-328,共4页Parenteral & Enteral Nutrition

摘　　要：目的:观察内毒素(LPS)刺激后大鼠肝致炎/抗炎细胞因子的表达,及钙通道阻滞剂(维拉帕米)在内毒素诱导的肝急性反应中对炎症因子的调控作用。方法:将24只SD大鼠随机分为A(对照)组、B(LPS)组和C(维拉帕米)组。B和C组分别给予等渗盐水和10 mg/kg维拉帕米,腹腔注射30 m in后,给予10 mg/kg内毒素腹腔注射,60 m in后,取大鼠肝匀浆和外周血。用酶联免疫吸附法(ELISA)测定肝组织以及血清中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和白细胞介素10(IL-10)。结果:内毒素可诱导大鼠肝和外周血中TNF-α和IL-6的高表达(P<0.01),而肝IL-10以及外周血清蛋白未见明显变化(P>0.05)。维拉帕米可抑制内毒素诱导大鼠肝和外周血中TNF-α和IL-6的高表达(P<0.01),增加肝组织和外周血中IL-10的表达(P<0.01),降低血中谷丙转氨酶、总胆红素、清蛋白水平(P<0.01)。内毒素可升高外周血和肝组织中TNF-α/IL-10以及血清中IL-6/IL-10(P<0.01),维拉帕米可降低肝和循环中TNF-α/IL-10、IL-6/IL-10的比值(P<0.01)。结论:维拉帕米可调节致炎因子和抗炎因子的表达,改善内毒素诱导的急性肝损伤,致炎/抗炎因子比值可反应机体炎症反应的程度。Objectives ：To evaluate the effect of calcium channel blocker （verapamil） on pro-inflammatory and/or anti-inflammatory cytokines in liver and systemic circulation. Methods ：24 Sprague-Dawley rats were divided into 3 group randomly： control （A）, LPS （B） and Verapamil （C）. LPS（ 10 mg/kg） was given intraperitoneally in B group. After 30 minutes of intraperitoneal administration of Verapamil （ 10 mg,/kg body weight）, the Sprague-Dawley rats were given an intraperitoneal injection of 10 mg/kg of LPS in C group. Sixty minutes after LPS exposure, the hepatic tissue and serum were collected and assayed for the level of pro-inflammatory cytokines （TNF-ct and IL-6 ） and anti-inflammatory cytokine （IL-10） with ELISA. Results：Compared with Control group, the hepatic and circulating level of TNF-α and IL-6 increased significantly（P 〈0.01 ） after LPS injection with the augment of serum ALT and TBIL（ P 〈 0.01 ）. The increases of TNF-α and IL-6 levels in tissue and circulation were depressed greatly by verapamil（ P 〈0.01 ） with the concentration of IL-10 being enhanced significantly （ P 〈0.01 ） both in circulation and in situ and the decrease of serum ALT, TBIL and albumin levels （ P 〈 0.01 ）. Conclusions：Calcium channel blocker （verapamil） may limit the early hepatic injury caused by LPS accompanied with the balance of pro- and anti-inflammatory cytokines in liver.

关 键 词：维拉帕米 致炎因子 抗炎因子 内毒素 急性肝损伤 

分 类 号：R96[医药卫生—药理学]