血管活性肠肽对大鼠内毒素性休克肠道损伤保护作用的研究  

Protective effects of vasoactive intestinal peptide on intestinal lesions induced by endotoxic shock in rat

作　　者：张育才[1] 杨丽萍[1] 汤定华[1] 张宇鸣[1] 

机构地区：[1]上海交通大学附属儿童医院急救中心上海交通大学儿童危重病研究所,200040

出　　处：《中华儿科杂志》2006年第5期369-373,共5页Chinese Journal of Pediatrics

摘　　要：目的探讨大鼠内毒素休克模型的肠道病变、血液TNF-α、IL-1β、IL-10改变和血管活性肠肽(VIP)的保护作用。方法28只成年SD大鼠随机分成3组:对照组(8只),内毒素休克组(10只)和血管活性肠肽干预组(10只)。内毒素休克组大鼠左侧颈外静脉注射内毒素10 mg/kg,血管活性肠肽干预组注射同量内毒素后,即刻注射血管活性肠肽5 nmol,对照组注射等容量生理盐水。各组于实验开始后1、2、4、6 h分别留取血液,用ELISA法测定TNF-α、IL-1β和IL-10水平。大鼠自然死亡和实验持续6 h时放血处死,留取小肠段,进行病理学检查。结果内毒素休克组和血管活性肠肽干预组血液TNFα-、IL-1β和IL-10水平与对照组相比呈现升高(P<0.05 orP<0.01),其中TNF-α于2 h时达到高峰点,IL-1β和IL-10持续升高至6 h时间点。血管活性肠肽干预组TNF-α和IL-1β升高幅度低于内毒素休克组,IL-10升高幅度高于内毒素休克组(P<0.01)。注射内毒素后小肠光镜和电镜下均显示肠段病变,内毒素休克组病变明显较血管活性肠肽干预组严重。结论血管活性肠肽可减轻内毒素休克大鼠肠道病变,其保护机制与下调促炎症细胞因子和上调抑炎症细胞因子的表达有关。血管活性肠肽是脓毒症休克治疗中有潜力的免疫调节物质。Objective Vasoactive intestinal peptide （VIP） is a neuro-peptide that can modulate immunity in several aspects. Previous reports showed that VIP attenuates the deleterious consequences of severe infection and septic shock by regulating production of inflammatory cytokines in immune activated cells. Intestine is one of the major organ of immune system and it may trigger multiple organ dysfunction syndrome in sepsis. The present study was planned to study the change of serum TNF-α, IL-β, IL-10 level and histopathological alteration of intestinal tract, and protective effects of VIP on endotoxic shock in rat. Methods Twenty eight SD rats were randomly divided into 3 groups, including control group （ 8 rats）, LPS shock group （10 rats）, and LPS ＋ VIP group （ 10 rats）. Endotoxic shock model was established by administration of a single dose of 10 mg/kg LPS in LPS shock group, a bolus of 5 nmol VIP intravenous injection following LPS in LPS ＋ VIP group. The rats in the control group were given the same volume of normal saline injection. Blood samples were taken at time points of 1, 2, 4, and 6 hours after intervention from each group for measuring the level of TNF-α, IL-β and IL-10 by ELISA. Pathological changes of the intestine were observed by light microscope and electron microscope at the animals death or at the end of the experiment. Results Serum TNF-α, IL-β and IL-10 levels elevated at each time point in LPS shock group and LPS ＋ VIP group （P 〈 0. 05 or P 〈 0. 01 ）. TNF-α concentration reached the peak level 2 h after LPS injection ; IL-β and IL-10 increased continuously till the end of the experiment. In LPS ＋ VIP group, TNF-α and IL-β elevated slightly and IL-10 increased significantly as compared with LPS shock group （P 〈 0. 01 ）. Leukocyte infiltration, ischemia, segmental hemorrhage or necrosis appeared in intestine under light microscope and cell swelling, cytoplasmic vacuoles and organelle damage were observed under electron microscope. However, pathological

关 键 词：血管活性肠肽 休克 脓毒性 肠 细胞因子类 大鼠 

分 类 号：R459.7[医药卫生—急诊医学]