二烯丙基硫化物可下调百草枯中毒大鼠肺组织核转录因子-κB蛋白及肿瘤坏死因子-αmRNA表达  

Inhibition of pulmonary nuclear factor -κB and tumor necrosis factor -α expression by diallyl sulfide in rats with paraquat poisoning

作　　者：曹玉芳[1] 李景辉[1] 欧宗兴[2] 殷宗宝[1] 陈栩栩[1] 韩艳丽[1] 宋维[3] 

机构地区：[1]海口市人民医院重症医学科,海南海口570208 [2]海口市人民医院呼吸科,海南海口570208 [3]海南省人民医院急诊科,海南海口570311

出　　处：《中华危重病急救医学》2015年第4期274-279,共6页Chinese Critical Care Medicine

基　　金：海南省自然科学基金（310143）

摘　　要：目的：探讨二烯丙基硫化物（DAS）对百草枯中毒所致大鼠急性肺损伤（ALI）的器官保护作用及抗炎机制。方法将80只雄性Wistar大鼠按随机数字表法分为对照组、模型组、地塞米松（DXM）治疗组及DAS治疗组，每组20只。一次性灌胃百草枯溶液70 mg/kg制备中毒模型；对照组灌胃等量生理盐水。制模后当日分别经腹腔注射DAS 100 mg/kg（DAS治疗组）、等量生理盐水（模型组）或DXM 1 mg/kg（DXM治疗组），均每日1次，共14 d。各组分别于制模后1、3、7、14 d随机处死5只大鼠，取右肺下叶行苏木素-伊红（HE）染色，光镜下观察肺损伤程度；取右肺上叶计算湿/干质量（W/D）比值，评价肺水肿程度；取右肺中叶,采用免疫组化检测核转录因子-κB（NF-κB）表达；取左肺采用反转录-聚合酶链反应（RT-PCR）检测肿瘤坏死因子-α（TNF-α）mRNA表达。结果① HE染色显示：对照组肺组织肺泡结构完整；模型组病理改变逐渐加重，肺泡壁结构破坏、肺间质水肿及大量巨噬细胞、中性粒细胞浸润，并伴有炎细胞移行至肺泡腔，部分肺泡腔内形成透明膜； DAS治疗组和DXM治疗组肺间质有部分增生、少量炎性细胞浸润，肺泡结构均无明显破坏。②肺W/D比值：模型组各时间点肺W/D比值明显高于对照组，3 d时达最高值（6.15±0.54比4.15±2.10，P＜0.05）；DAS治疗组和DXM治疗组各时间点肺W/D比值明显低于模型组，以3 d为明显（3.99±1.26、4.30±0.70比6.15±0.54，均P＜0.05）；而DAS治疗组与DXM治疗组比较均无明显差异。③免疫组化显示：对照组细胞质有极少量NF-κBp65阳性表达；模型组细胞核中有较多NF-κBp65阳性表达；DAS治疗组和DXM治疗组细胞质中有少量NF-κBp65阳性表达，细胞核中无明显NF-κBp65阳性表达。积分A值明显低于模型组，以3 d为明显〔（17.98±0.06）×107、（18.53±0.04）×107比（28.85±0.61）×107ObjectiveTo investigate the mechanism of anti-inflammatory effect of diallyl sulfide （DAS） in protection against acute lung injury （ALI） in rats with paraquat poisoning.Methods Eighty male Wistar rats were randomly divided into four groups, namely： control group, model group, dexamethasone （DXM） treatment group, and DAS treatment group, with 20 rats in each group. The model of paraquat poisoning was reproduced by single does of 70 mg/kg given by gavage, while the same volume of normal saline （NS） was given in same manner in control group. 100 mg/kg of DAS, the same volume of NS, or 1 mg/kg DXM injection were given respectively in DAS treatment group, model group, or DXM treatment group intraperitoneally after exposure to paraquat, once a day for 14 days.＆amp;nbsp;Five rats in each group were sacrificed at 1, 3, 7, 14 days, respectively. The inferior lobe of right lung was harvested, and the degree of lung injury was observed with hematoxylin and eosin （HE） staining under optical microscope; the upper lobe of right lung was used to determine the lung wet/dry weight （W/D） ratio and for evaluation of the degree of pulmonary edema. The expression of nuclear factor -κB （NF-κB） in the middle lobe of right lung was assessed with immunohistochemistry. The expression of tumor necrosis factor -α （TNF-α） mRNA in the left lung was determined with the reverse transcription-polymerase chain reaction （RT-PCR）.Results① The pulmonary structure in control group was found to be intact. However, in the model group there were progressive pathological changes in lung, including marked edema and thickening of alveolar walls, collapse of alveoli, infiltration of inflammatory cells, alveolar wall, and obvious bleeding in the local lung tissue, and formation of transparent membrane in alveolar space. Less infiltration of inflammatory cells and no obvious destruction were found in alveolar structure in the DAS and DXM treatment groups.② Lung W/D ratio： lung W/D ratio of model group was appa

关 键 词：百草枯 中毒 核转录因子-ΚB 肿瘤坏死因子-Α 急性肺损伤 二烯丙基硫化物 

分 类 号：R595.4[医药卫生—内科学]