目的 探讨卡托普利对全氟异丁烯(PFIB)急性吸入性肺损伤的保护作用及其机制.方法 采用实验室自制的全身暴露动态染毒系统对实验大鼠进行吸入染毒.48只雄性Wistar大鼠随机分为正常对照组、卡托普利药物对照组、PFIB染毒对照组和PFIB染毒+低、中、高剂量卡托普利治疗组(n=8).其中PFIB染毒各组染毒剂量为260 mg/m3×5 min,正常对照组和卡托普利药物对照组于过滤空气中暴露5 min.卡托普利低、中、高各组给药剂量分别为31.5、63和126 mg/kg,染毒后15 min及3、6、9 h分别腹腔注射给药1次;卡托普利药物对照组于相同时间点腹腔注射卡托普利剂量为126 mg/kg;正常对照组、PFIB染毒对照组于相同时间点腹腔注射相应体积的生理盐水.记录各组大鼠染毒后24 h存活数,制备支气管肺泡灌洗液(BALF),留存肺组织样本,测定肺系数、BALF中蛋白和磷脂含量,以及肺组织匀浆中脂质过氧化物(LPO)含量,制备肺组织病理切片并进行组织病理学检查.结果 与正常对照组相比,PFIB染毒后24 h大鼠各项肺系数、BALF中蛋白及磷脂含量、肺组织匀浆中LPO含量均显著升高(P<0.05),卡托普利治疗后,PFIB染毒+低、中、高剂量卡托普利各组肺系数、BALF中蛋白及磷脂含量、肺组织匀浆中LPO含量均显著降低(P<0.05),卡托普利药物对照组未见明显改变.组织病理学结果显示,卡托普利治疗后各组大鼠肺损伤程度明显缓解,且具有剂量依赖性.结论 卡托普利治疗可明显改善PFIB吸入性急性肺损伤,其作用机制可能与其对氧化还原系统的保护作用有关.

急性肺损伤(ALI)是一种急性低氧性呼吸功能不全综合征;其容易发展为急性呼吸窘迫综合征(ARDS).肾素-血管紧张素系统(RAS)被证实与ALI/ARDS发生发展密切相关.RAS的经典轴——血管紧张素转化酶(ACE)-血管紧张素(Ang)Ⅱ-AngⅡ1型受体(AT1R)轴通过诱导过度炎症反应、损伤肺泡屏障功能、触发凝血功能障碍等机制,诱导ALI/ARDS.RAS的ACE2-Ang(1-7)-Mas轴具有拮抗ACE-AngⅡ-AT1R轴的作用,通过抑制炎症反应、拮抗氧化应激、降低肺血管渗透性等机制,改善ALI/ARDS.ACE抑制剂、降低Ang Ⅱ水平的药物、AT1 R阻断剂、AT2R兴奋剂、重组ACE2、过表达ACE2的间充质干细胞、Ang1～7和脂氧素A4等,已被动物实验证实对ALI/ARDS有改善作用.这为防治ALI/ARDS、改善预后提供了新靶点.

大规模突发化学事件一旦发生,往往在短时间内有大量伤员和事件受害者以各种方式涌入医院,对医院的应急处置能力形成冲击.与其他突发事件不同,因涉及有毒有害化学品,突发化学事件的处置具有其特殊性.在应对大规模突发化学事件时,医院及救护人员应认识到:做好急救人员自身防护是施救的前提,应开设洗消区维护设施安全和人员健康,检伤分类可最优化使用现有医疗资源,启动紧急入院程序可加速救治流程,应按照化学毒剂以及确定性治疗措施进行急诊处置,伤员运输必须确保及时通畅,同时还应重视对事件经历者的心理干预问题.

目的 研究细胞外组蛋白在急性呼吸窘迫综合征(ARDS)发病过程中的变化,探索其具体作用及临床价值.方法 通过氯气染毒复制小鼠ARDS模型,在不同浓度氯气染毒条件下,检测血浆中细胞外组蛋白H4、血管内皮细胞损伤标志物sTM、肺组织病理的改变;分析组蛋白H4与sTM的关系.结果 正常小鼠血浆中组蛋白H4的平均浓度为(0.76±0.17) μg/ml;氯气染毒后,小鼠血浆中组蛋白H4水平升高;当200 ppm氯气染毒(30min)后12h,血浆中组蛋白H4的平均浓度为(7.68±2.47) μg/ml.氯气浓度越高,血浆中组蛋白升高越明显,二者具有明显的正相关性.在氯气吸入损伤中,血浆中内皮损伤标志物sTM也明显升高,且与血浆中组蛋白H4具有明显的相关性(r=0.830 2).HE染色镜下可见,染毒小鼠肺组织炎症细胞浸润,肺泡间隔增宽,肺泡上皮细胞和血管内皮细胞肿胀,且随氯气浓度增高损伤加重.结论 细胞外组蛋白在氯气所致ARDS小鼠血浆中明显升高,且与肺损伤程度密切相关,提示其可能在ARDS发病机制中起重要作用.

及时有效地救治化学品中毒事件的伤员是公共卫生应急救援领域的重要课题.以色列拥有较为发达的化工产业,而且自建国以来历经多次战争、众多不同规模的局部冲突以及各类恐怖袭击的"考验",逐步建立了一套可有效应对大规模化学中毒事件伤员处置的响应机制.该文综述了以色列应对大规模化学袭击事件的国家准备计划和相应的战略储备方案,以及大规模化学中毒事件伤员救援的院前处置流程,以期为我国应对同类型事件的伤员救援提供参考和借鉴.

Background: Chlorine gas (Cl 2 ) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl 2 is very high, mainly because the pathogenesis of ARDS remains unclear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present study aimed to examine the pathogenic role of histone H4 in Cl 2 -induced ARDS. Methods: ARDS was induced by Cl 2 exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury (ALI). Histone H4 or anti-H4 antibody was administered through the tail vein 1 h prior to Cl 2 exposure to study the pathogenic role of histone H4. Toll-like receptor 2 knock-out ( Tlr2 -KO) and Tlr4 -KO mice were used in conjunction with blocking antibody against TLR1, TLR2, TLR4, or TLR6 to explore the mechanism involved in histone H4-mediated injury. Results: Cl 2 exposure induced a concentration-dependent ALI. The levels of circulating histone H4 were positively correlated with Cl 2 concentrations. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration, while anti-H4 antibody showed protective effects. Tlr4 deficiency improved lethality rate, blood gas, and pulmonary edema, and prevented endothelial and neutrophil activation caused by Cl 2 exposure. More importantly, Tlr4 gene deletion greatly diminished the effect of histone H4 or anti-H4 antibody observed in wild-type (WT) mice. The impact of Tlr2 on inflammatory injury was not significant. The role of TLRs was also validated by endothelial activation mediated by histone H4 in vitro. Conclusions: Circulating histone H4 played a pro-inflammatory role in ARDS caused by Cl 2 . TLR4 was closely involved in histone H4-mediated inflammatory injury. Therefore, intervention targeting histone H4 is potentially protective.

[目的]建立紫外分光光度法测定全血胆碱酯酶活性测定试纸(简称测酶试纸)中溴化乙酰胆碱含量的方法,并验证该方法的可行性.[方法]利用溴化乙酰胆碱和溴百里香酚蓝(测酶试纸的两种主要成分)的溶解性差异,将测酶试纸中的溴化乙酰胆碱洗脱下来,以浓度为2.8、5.6、8.4、11.2、14.0 mmol/L的溴化乙酰胆碱对照品溶液制作测酶试纸中溴化乙酰胆碱含量测定方法的标准曲线,并对该法的标准曲线线性、准确度、精密度、耐用性及回收率进行验证.[结果]该方法的标准曲线线性良好,线性相关系数的平均值为0.999 79.该法的准确度、精密度和耐用性良好,批内和批间相对标准偏差均不超过4％,加样回收率在94.90％～106.22％之间.[结论]该方法可用于测定测酶试纸中溴化乙酰胆碱的含量.

急性肺损伤(ALI)是一种由多种免疫细胞共同介导的过度、失控的肺部炎症反应.作为肺免疫系统的主要作用细胞和肺炎症微环境的重要组成部分,肺泡巨噬细胞(AM)是对抗ALI的第一屏障,在ALI发生发展的不同病理阶段发挥重要作用,扮演促炎和抗炎的双重角色.本文就AM的起源、极化、功能及其在ALI中作用的研究进展进行简要概述.

Objective: Sulfur mustard (SM) is a vesicant alkylating agent. There are still biochemical mechanisms underlying SM damage that are unknown. This study was to determine the differences of apoptosis and pulmonary fibrosis underlying SM-induced acute pulmonary injury via intraperitoneal injection and intratracheal instillation in rats. Methods: An acute pulmonary injury model was established in a preliminary experiment using intraperitoneal injection and intratracheal instillation of SM in rats, in order to determine the equal toxicity dose of SM (1LD50). Then, SM-induced changes in apoptosis and pulmonary fibrosis were observed by immunohistochemical staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Masson staining and electron microscopic observationin intraperitoneal and tracheal SM groups that were injected intraperitoneally and instilled intratracheally with diluted SM [0.1 mL per rat (0.98 LD50 = 2 mg/kg)] and SM [0.1 mL per rat (0.96 LD50 = 8 mg/kg)] respectively, and an untreated control group. Results: In the alveolar septum, the positive expression ratio of apoptotic cells, Bax, caspase-3, and caspase-9 by TUNEL and Immunohistochemistry (streptavidin-perosidase method) in the intraperitoneal SM group was increased compared with the tracheal SM group (P < 0.05), but a significantly lower positive expression ratio of Bcl-2 was detected (P < 0.05). Electron microscopic observations confirmed that the type I and II alveolar epithelial cells in lungs exhibited apoptotic morphologic features, such as cracked, lost, and disordered microvilli of membranes, fuzzy mitochondrial cristae, and detached, dissociated ribosomes from the surface of the rough endoplasmic reticulum. A significantly higher positive expression ratio of MMP-2, MMP-9, TIMP-1, TIMP-2, collagen type I, collagen type III, TGF-beta 1, and Smad7 by immunohistochemical staining in the alveolar septum were detected in the intraperitoneal SM group compared with the tracheal SM group (P < 0.05). Conclusions: These data demonstrated increased apoptosis and pulmonary fibrosis via intraperitoneal injection under equal toxicity doses SM (1LD(50)) in rats.

This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD50=8mg/kg) and SM (0.98 LD50=2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD50 doses.

Lung is the main target of lung-damaging agents(or choking agents,lung irritants)which can result in potential permanent respiratory depression,the rapid development of acute lung injury(ALI)and pulmonary edema,even death in severe cas-es. Recently,with the research progress in the pathogenesis of lung-damaging agents,numerous corresponding experimental studies were carried out and some progress were made. This paper summarizes the progress in the study of lung-damaging agents on the re-search situation,pathogenic mechanism and biomarker,to provide reference for the promotion of ALI prevention,medical antagonis-tic measures and clinical treatment.

Objective To establish rat model of sulfur mustard (SM)-induced acute lung injury via intraperitoneal and tracheal injection, in order to compare the differences of pulmonary fibrosis indexes. Methods A total of 136 male Sprague Dawley rats were randomly divided into the five groups, i.e. the control group with 8 rats and other four groups (intraperitoneal SM group, intraperitoneal propylene glycol group, tracheal SM group and tracheal propylene glycol group) with 32 rats in each group. The rats in the intraperitoneal SM group were intraperitoneally injected with 0.1 ml diluted SM (0.96 LD50 = 8 mg/kg), the rats in the tracheal SM group were intratracheally injected with 0.1 ml diluted SM (0.98 LD50=2 mg/kg), the rats in the intraperitoneal propylene glycol group and the tracheal propylene glycol group were injected with 0.1 ml propylene glycol through peritoneal cavity and trachea respectively; meanwhile the status quo was kept with the normal control group. SM-induced pulmonary fibrosis indexes were observed by Masson and immunohistochemical staining. Results Light microscopic observation confirmed that green-stained collagen fibers increased in the alveolar septa at 72nd h. Significantly higher positive expression rates of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemical staining in the alveolar septa were detected in the intraperitoneal SM groups compared with those in the tracheal SM groups at each period of time ( < 0.05). The positive expression rates of type Ⅰ collagen and type Ⅲ collagen in the alveolar septa in the intraperitoneal SM groups were significantly increased compared with those in the tracheal SM group at each period of time ( <0.05). Significantly higher positive expression rates of TGF-β1 and Smad7 in the alveolar septa were also observed in the intraperitoneal SM group compared with the tracheal SM group at each period of time ( < 0.05). Conclusions When LD50 concentration of SM through intraperitoneal injection is similar to that through tracheal injection in rat, the indexes of pulmonary fibrosis are significantly increased after intraperitoneal injection compared with those after tracheal injection, suggesting that SM-induced pulmonary fibrosis can be more easily induced through intraperitoneal injection.

Objective To study the change rule of MMP-2 and MMP-9 during the process of acute lung injury in rats induced by perfluoroisobutylene (PFIB) inhalation,evaluate the therapeutic effect of tetracycline hydrochloride (TET) on acute lung injury (ALI) induced by PFIB,analyze its mechanism and provide reference for clinical prevention and treatment of chemical lung injury.Methods Wistar rats were exposed to gaseous PFIB in a whole body exposure system,take the samples of bronchoalveolar lavage fluid (BALF) and lung tissues for the detection of lung coefficient,protein and phosphatide contents in BALF,meanwhile,the activity of MMP-2 and MMP-9 in BALF and lung tissue were also detected by zymography analysis technique.Results The results showed that the sub-lethal dose PFIB-inhalation could induce typical ALI;the activities of MMP-2 and MMP-9 in normal rat lung tissue and BALF were extremely low,but MMP-2 and its precursor pro-MMP-2 were all significantly increased in lung tissue and BALF of PFIB exposed rats,the MMP-9 was only observed some upward trend no statistical significance.TET could significantly alleviate the ALI induced by PFIB and dose-dependently inhibit the activity of MMP-2 in lung tissue and BLAF,high dose of TET could reduce MMP-2 and pro-MMP-2 to normal levels.Conclusion The results showed that the upward expression of pro-MMP-2 and MMP-2 both in lung tissue and BALF of PFIB-inhaled rats was highly consistent with the course of ALI;while TET could reduce the expression of pro-MMP-2 and MMP-2 in lung tissue,alleviate lung injury,which suggested that these two kinds of MMPs may play an important role in ALI induce by PFIB inhalation.

Vesicants are the main agents used to fill chemical weapons, and chemical weapons abandoned by the Japa-nese Army in China.The mustard-lewisite mixture, which was developed for cold weather or high-altitude use due to its lower freezing point, is a special and important agent.The toxicology, emergency treatment and clinical management of mustard-lewisite mixture poisoning are introduced in this paper.

In the management of disasters of any kinds,including the catastrophic chemical disasters,the contingency plan is,definitely,a saga for the efficient practice of the detailed and technically sophisticated rescue work,which is a guarantee for mini?mizing the negative impacts and loses of various kinds induced by the disaster. Backgrounded on the“Tianjin Port 8 · 12 Catastrophic Explosion Accident”,which was heavily involved with large amounts of chemicals of many kinds,key planning factors to be consid?ered in making the contingency plan for the emergency medical response team are discussed,and suggestions for some of the details within a certain kind of a plan are also provided.

目的 经腹腔和气管建立大鼠芥子气(SM)肺损伤的动物模型,比较两种大鼠急性肺损伤模型炎性反应的差异.方法 选取Sprague Dawley大鼠136只,分为5组,正常对照组8只,其他4个组(腹腔SM组、腹腔丙二醇对照组、气管SM组、气管丙二醇对照组)每组32只.腹腔SM组腹腔内注入稀释的SM 0.1 mL(0.96 LD50＝8 mg/kg),气管SM组气管内注入稀释的SM 0.1 mL(0.98 LD50 =2 mg/kg),正常对照组不做任何处理.ELISA法检测支气管肺泡灌洗液和血液标本,HE染色和免疫组织化学判断炎性反应情况.结果 腹腔SM组各时间段支气管肺泡灌洗液蛋白含量和细胞计数与气管SM组相比显著升高(P＜0.05);腹腔SM组各时间段血清TNF-α、IL-1β、IL-6与气管SM组相比显著升高(P＜0.05);腹腔SM组各时间段肺泡间隔T、B淋巴细胞和巨噬细胞阳性表达率与气管SM组相比显著增加(P＜0.05).结论 大鼠在SM LD50相似的情况下,腹腔SM组支气管肺泡灌洗液、肺泡间隔及血清炎性反应指标明显高于气管SM组.

To deal with effectively acute chemical injury events,the service ability of protective medicine against chemical weapons has being widened from dealing with traditional chemical warfare to public chemical accident or chemical terrorist attack. Fo?cusing on the important researching and developing of medicine for chemical defense use only,the novel drug/device combination products should be vigorously promoted including the new mechanism,good curative effect and high safety of detoxification drugs such as hydroxycobalamin used in the treatment of known or suspected cyanide poisoning in both adults and the pediatric population ,and the convenient and quick drug delivering technologies such as auto-injectors with a retreat hidden needle and a smart remindful injec?tion,which could improve greatly the emergency medical rescue ability of chemical accidents.

目的 应用表面增强拉曼光谱法检测相关样品内百草枯含量,探究大容量全肺灌洗术对肺组织内百草枯清除效能.方法 选用SPF级Wistar大鼠,60 mg/kg为染毒剂量,经口一次灌胃染毒制备动物模型,于染毒后相应时间点采血,行大容量全肺灌洗术留取肺泡灌洗液,留取肺组织.应用表面增强拉曼光谱法检测血浆、肺泡灌洗液及肺组织中百草枯含量,并进行统计分析.结果 各时间点(1 ～168 h)血浆、肺泡灌洗液、肺组织匀浆中均检测到百草枯;染毒后1h血浆、肺泡灌洗液中百草枯含量达峰值(分别是8 926.3±1 586.47和1 573.9±310.13 ng/ml),12 h肺组织中百草枯达峰值(13 642.2±1 242.66 ng/g),15h时肺泡灌洗液中百草枯含量出现第二高峰;各组灌洗侧(左侧)肺组织内百草枯浓度低于未灌洗侧(右侧),清除率为40％±12％.结论 大容量全肺灌洗术对肺组织内百草枯有较高的清除效能,可作为清除肺组织内百草枯一项救治措施.

Objective To establish animal model of sulfur mustard (SM)-induced acute lung injury in rats via intraperitoneal and tracheal injection,in order to compare the difference of oxidative stress reaction.Methods 136 male Sprague Dawley rats were selected and randomly divided into five groups,the control group with eight cases,other four groups (i.e.the intraperitoneal SM group,the intraperitoneal propylene glycol group,the tracheal SM group,the tracheal propylene glycol group) with 32 cases in each group.The rats in intraperitoneal SM group were injected intraperitoneally with diluted SM 0.1 ml (0.96 LD50 =8 mg/kg),the rats in tracheal SM group were injected intratracheally with diluted SM 0.1 ml (0.98 LD50 =2 mg/kg),meanwhile the status quo was kept with the normal group.SM-induced oxidative stress was observed by enzyme linked immunosorbent assay and immunohistochemical staining.Results In bronchoalveolar lavage fluid,lactate dehydrogenase and glutathione peroxidase levels in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group (all P ＜0.05).Serum γ-glutamyl transpeptidase and thobarbituric acid reactive substances levels in the intraperitoneal SM group at a period of time were higher than those in the tracheal SM group (all P ＜0.05).In the alveolar septum,the positive expression ratios of 8-hydroxy deoxyguanosine,nuclear factorE2 related factor 2 and heme oxygenase-1 in the intraperitoneal SM group at a period of time were increased compared with the tracheal SM group (all P ＜0.05).Conclusions Under similar concentration of SM via intraperitoneal and tracheal injection in rats,indexes of lung oxidative stress in the intraperitoneal injection are increased compared with the tracheal injection,which may be related to fast absorption of the peritoneal cavity to SM.

OBJECTIVE To investigate the change of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),intercellular adhesion molecules(ICAM-1),matrix metalloproteinases 2 (MMP-2) and MMP-9 contents in cultured pulmonary microvascular endothelial cells (PMVECs) in rats after perfluoroisobutylene (PFIB) exposure. METHODS PMVECs were separated and purified using a modified method of implantation of pulmonary tissues. After identification,PMVECs were divided into the normal control group and the PFIB-exposed groups(n=3). The PFIB-exposed groups inhaled PFIB at the concentration of 200 mg · m-3 for 5 min in a flow-past header,while the normal control group were PMVECs in quiescent condition. The supernatants and lysates of PMVECs were harvested at 0.5,1,2,4 and 8 h,respec?tively, after execution. The contents of TNF-α,IL-1β,ICAM-1,MMP-2 and MMP-9 were measured by ELISA,and the activity of MMP-2 and MMP-9 was measured by gelatin zymography. RESULTS① According to the morphologic characteristics of cell growth and the expression of specificity antigens and the bind experiment of phytohemagglutinin,the cells separated and purified by modified method shared the characteristics of PMVECs.②TNF-αwas rapidly expressed by PMVECs at 0.5 h post PFIB stimulation and the maximum value was achieved at 2 h post PFIB stimulation(P<0.05). The newly synthesized TNF-α was slowly released out of the cells. The maximum TNF-α in the supernatant was achieved at 4 h post stimulation.③Within 2 h of stimulation,PMVECs synthesized a large amount of IL-1β and peaks at 2 h. However,IL-1βwas never released to the extracellular milieu.④The amount of ICAM-1 was rapidly synthesized by PMVECs after PFIB stimulation,but at a low level.⑤After stimulation with PFIB,MMP-2 in the supernatant of PMVECs culture was gradually increased,peaked at 2 h and then decreased subsequently. The biological activity of MMP-2 in the supernatant was also enhanced after PFIB stimulation. PFIB did not stimulate synthesis or secretion of MMP-9,indicating that PMVECs were not the main source of MMP-9 during PFIB inhalation-induced acute lung injury. CONCLUSION PFIB stimulates the surviving PMVECs to synthesize a large amount of TNF-α,IL-1β, MMP-2 and conjunctive ICAM-1.