中性粒细胞凋亡在烧伤兔急性肺损伤发病中的作用

目的:探讨中性粒细胞(PMN)凋亡在急性肺损伤(ALI)发病中的作用。方法:健康新西兰大白兔36只,随机分为对照组6只和烧伤组30只;烧伤组又随机分为5组,分别在烧伤后2、4、8、12、24 h 5个不同时间点处死动物,每次6只;共计6组,每组6只。观察烧伤组不同时间点兔肺组织病理,进行肺损伤评分,计算肺湿干重比(W/D),分离纯化肺泡灌洗液中的PMN,用流式细胞仪定量检测PMN凋亡和坏死细胞和呼吸爆发。结果:烧伤组各时相点均可见到肺泡腔及间质内白细胞渗出、浸润,肺泡腔内见渗出液,肺泡隔增厚,肺泡及间质充血,部分肺泡塌陷、不张,透明膜形成,且随时间延长病变加重,肺损伤的半定量评分增加(P0.01),尽管各时间点组间差异无统计学意义(P0.05),但与对照组比较差异均有统计学意义(P0.05～P0.01)。烧伤组肺W/D也随时程延长而升高(P0.01),8 h后高于对照组(P0.01);兔烧伤后2～12 h,肺灌洗液中PMN凋亡率显著降低(P0.01);PMN坏死率在烧伤后2 h显著升高(P0.05),4 h达峰值(P0.01),8 h后下降至对照组水平(P0.05);烧伤组PMN的存活率均显著高于对照组(P0.01);PMN呼吸爆发在烧伤2 h后升高,8 h到达峰值(P0.01),后下降至对照组水平。结论:ALI兔PMN从血管游出到达肺组织,在肺泡中大量聚集,且凋亡途径发生障碍,致PMN持续处于活化状态,与ALI的发病相关。     

中性粒细胞凋亡延迟在脂多糖所致大鼠急性肺损伤发病机制中的作用

目的 探讨急性肺损伤时肺组织及外周血中性粒细胞（PMN）凋亡和坏死的发生规律及其与肺损伤的关系。以及可能涉及的机制。方法 Wistar大鼠50只,腹腔注射脂多糖（LPS,O55B5,3mg/kg)造成大鼠急性肺损伤,分为LPS注射后2h组、4h组、8h组,12h组及正常对照组。于预定时相取血及支气管灌洗液,密度梯度离心分离PMN,用流式细胞仪测定凋亡,坏死细胞比例及呼吸焊发功能,同时测定乳酸脱氢酶（LDH）含量,肺通透指数,肿瘤坯 煞费苦心因子（TNF）、白细胞介素（IL）1β、IL-6含量和Ca^2 浓度。结果 ALI大鼠肺灌洗液中PMN凋亡,坏死比例的变化与外周血不同,主要表现为存活细胞比例增加,凋亡延迟,肺灌洗液中TNF、IL-1β、IL-6含量明显高于外周血,且持续时间较长,同时,肺灌洗液LDH明显升高,肺通透指数显著增加。结论 肺组织中高浓度的细胞因子和短暂升高的Ca^2 使游出的PMN的正常凋亡途径发生障碍,造成PMN持续处于激活状态及毒性内容物的持续释放,与肺组织损伤有密切关系。     

内毒素急性肺损伤与中性粒细胞凋亡研究现状

内毒素（endotoxin）是革兰阴性菌细胞壁的脂多糖（lipopolysaccharide,LPS）成分,细菌死后细胞壁崩解时释出。内毒素可诱导肺泡巨噬细胞和上皮细胞产生多种细胞因子、趋化因子和激活中性粒细胞（polymorphonucler neutrophil,PMN）并使其向损伤部位聚集,导致急性肺损伤（acute lung injury,ALI）和急性呼吸窘迫综合征（acute respira-tory distress syndrome,ARDS）。现有资料表明PMN凋亡延迟在急性肺损伤的发生过程中起到重要作用,了解PMN凋亡调控有利于调节机体炎症反应,可为ALI开辟新的治疗路径。     

中性粒细胞在急性肺损伤中的作用的研究进展

急性肺损伤(ALI)是临床常见危重症,急性呼吸窘迫综合征(ARDS)是ALI的严重阶段,是导致危重患者死亡的主要原因。ALI/ARDS主要是紊乱的炎症反应的结果,其中中性粒细胞在ALI/ARDS的发生发展过程中起到了至关重要的作用。由于涉及的炎症机制复杂、治疗困难,目前ALI/ARDS危重患者的病死率仍居高不下。因此,深入研究炎症机制是突破ALI治疗瓶颈的前提。本文就中性粒细胞参与ALI炎症反应及肺组织修复的机制进行综述。     

中性粒细胞在高浓度氧诱发急性肺损伤中的作用

目的:测定鼠支气管肺泡清洗液中细胞成分,阐明高浓度氧诱发急性肺损伤的发生机制。方法:20只雄性6周龄[(226±53.6)g]Wistar鼠被分为3组:(1)对照组(空气中饲养,n=6)。(2)实验组1(暴露在90%～95%氧气中24～48h,n=7)。(3)实验组2(暴露在90%～95%氧气中72h,n=7)。实验中动物可自由进食和水。结果:与对照组相比,实验组2的支气管肺泡清洗液中总细胞数减少[(3.81±0.35)×105/ml,(2.53±0.77)×105/ml];巨噬细胞数减少[(3.80±0.36)×105/ml,(2.09±0.59)×105/ml];而中性粒细胞计数明显增多[0,(43.56±42.63)×103/ml]。实验组2的动物都出现双侧胸水。结论:中性粒细胞动员并进入肺组织是高浓度氧诱发急性肺损伤的明显特征,损伤的发生与暴露时间有关。提示早期抑制中性粒细胞进入肺组织是治疗高浓度氧诱发急性肺损伤的重要途径。     

整合素在急性肺损伤中作用与机制的研究进展

急性肺损伤及急性呼吸窘迫综合征死亡率高,其发生机制研究备受关注。整合素广泛表达于细胞表面,与急性肺损伤密切相关。本文对急性肺损伤时整合素家族在调节炎症细胞招募、炎症因子释放和肺泡毛细血管通透性等方面的作用进行综述。     

粒细胞-巨噬细胞集落刺激因子在急性肺损伤发病机制中的研究进展

急性肺损伤（ALI）是机体炎症介质过度表达导致的自身破坏性反应的结果。最近研究表明，粒细胞-巨噬细胞集落刺激因子（GM-CSF）与肺泡巨噬细胞功能、肺宿主防御反应、表面活性物质稳态有关。在ALI发病机制中，GM-CSF能影响炎症和细胞凋亡调控及其信号转导途径。作者对此作一综述。     

急性肺损伤中性粒细胞凋亡异常及甲基强的松龙调控的研究

目的 探讨急性肺损伤时支气管肺泡灌洗液(BALF)中的中性粒细胞(PMN)凋亡发生规律及甲基强地松龙调控关系.方法 豚鼠30只,分为3组1组生理盐水正常对照组,2组油酸致病组,3组油酸+甲基强的松龙组.组2、组3分别由尾静脉注射油酸(0.12 mL/kg)造成豚鼠急性肺损伤模型.组1则注入生理盐水.油酸+甲基强的松龙组在实验造模前2 d由腹腔注射甲基强地松龙0.10 mg/kg体质量,1次/d.组1、组2、组3分别于注射后2 h用生理盐水进行全肺支气管肺灌洗,收集BALF.用梯度密度法离心收集PMN.用原位末端标记法检测BALF中PMN凋亡.结果 油酸致病组、油酸+甲基强的松龙组和正常对照组BALF中PMN凋亡百分比分别是(2.500±1.080)%、(4.200±1.033)%和(6.400±1.505)%.油酸致病组、油酸+甲强龙组较正常对照组BALF中PMN凋亡均显著降低(均P＜0.01).结论 急性肺损伤炎性细胞PMN凋亡延迟,PMN持续激活和释放毒性内容物与肺损伤有密切关系.甲基强地松龙能调控干预急性肺损伤时PMN凋亡延迟.     

体外循环手术中性粒细胞致肺损伤的机制

在体外循环（extracorporeal circulation，ECC）手术开展的早期，外科医生就发现ECC术后存在肺功能障碍，主要表现为肺泡-动脉血氧分压梯度增加、肺水肿、肺顺应性下降和肺血管阻力增加，临床上的表现差异很大。随着对ECC基础和临床研究的不断深入，多数学者认为ECC引起的全身性炎症反应是导致ECC术后肺损伤的首要因素^[1]。     

凉膈散对内毒素致急性肺损伤大鼠中性粒细胞凋亡的影响*

目的：观察凉膈散对内毒素（LPS）致急性肺损伤（ALI）大鼠肺组织病理学及血中性粒细胞（PMN）凋亡的影响。方法：选取健康雄性SD大鼠72只,随机分为6组,每组12 只,分别为正常对照组、ALI模型组、凉膈散大剂量组、凉膈散中剂量组、凉膈散小剂量组和强的松治疗组。给予正常对照组大鼠气管内滴注生理盐水,其余各组大鼠均气管内滴注LPS,每天一次,连续2天,气道内滴注1小时后分别以生理盐水、凉膈散不同剂量、强的松灌胃,每天2次。分别于第二次气管滴注后12小时、24小时每组处死6只。取外周血中性粒细胞,流式细胞仪检测PMN的凋亡改变。结果 ：病理学积分：12h模型组（2.08±0.12）高于正常对照组（0.33±0.03）（P<0.01）, 12h凉膈散大剂量组（0.83±0.09）、中剂量组（1.00±0.09）、小剂量组（1.17±0.08）均低于模型组（2.08±0.12）(P<0.01或P<0.05),24h模型组（2.25±0.11）高于正常对照组（0.41±0.04）（P<0.01）,凉膈散大剂量组（0.67±0.05）、中剂量组（1.17±0.07）、小剂量组（1.33±0.06）均低于模型组（2.25±0.11）(P<0.01或P<0.05)。中性粒细胞凋亡指数：12h模型组（51.36±3.99）低于正常对照组（71.71±4.13）（P<0.01）, 12h凉膈散大剂量组（66.37±4.25）、中剂量组（61.6±5.02）高于模型组（51.36±3.99）(P<0.05), 24h模型组（63.04±4.89）低于正常对照组（80.82±5.19）（P<0.01）, 凉膈散大剂量组（71.32±5.32）高于模型组（63.04±4.89） (P<0.05)。结论：凉膈散可诱导急性肺损伤时的中性粒细胞凋亡,抑制中性粒细胞发挥活性作用, 从而减轻急性肺损伤肺部炎症反应,推测其机制可能是通过抑制NF- κB表达。     

Protective Effect of Curcumin on Endotoxin-induced Acute Lung Injury in Rats

Acute lung injury (ALI) or its more severe form, the acute respiratory distress syndrome (ARDS), is a common, devastating clinical syndrome that affects both medical and surgical patients. The most common cause of ALI is sepsis. There is now well-documented evidence that pulmonary inflammation contributes to the devel-opment of ALI. Despite significant advances in our un-derstanding of pathophysiology and technologies in the supportive management, mortality from ALI remains excessive. C…     

胆碱能抗炎通路在急性肺损伤中的作用研究进展*

In view of the complex etiology and pathogenesis, the mortality of acute lung injury remains high, which seriously threaten human health and affect the quality of life. Studies in recent years found that cholinergic anti-inflammatory pathway (CAP) played an important role in the course of systemic inflammatory reaction. Its mechanism is related to inhibit the inflammatory response synthesis by suppressing vagus nerve to release proinflammatory cytokines. As a central player in the cholinergic anti-inflammatory pathway, Alpha 7 nicotinic acetylcholine receptor (α7nAChR) can negatively regulate ALI caused by many factors. The present review focuses on the anti–inflammatory mechanism of acute lung injury.     

Protective Effect of Genistein on Lipopolysaccharide-induced Acute Lung Injury in Rats

Summary： To investigate the protective effect of genistein on endotoxin-induced acute lung injury in rats, and explore the underlying mechanisms, 32 male Sprague-Dawley rats were randomly divided into 4 experimental groups： saline control, genistein alone, lipopolysaccaride alone, and genistein pretreatment. Each treatment group consisted of eight animals. Animals were observed for 6 h after LPS challenge, and the wet/dry （W/D） weight ratio of the lung and bronchoalveolar lavage fluid （BALF） protein content were used as a measure of lung injury. Neutrophil recruitment and activation were evaluated by BALF cellularity and myeloperoxidase （MP（）） activity. RT-PCR analysis was performed in lung tissue to assess gene expression of ICAM-1. The histopathological changes were also observed using the HE staining of lung tissue. Our results showed that lung injury parameters, including the wet/dry weight ratio and protein content in BALF, were significantly higher in the LPS alone group than in the saline control group （P〈0.01）. In the LPS alone group, a larger number of neutrophils and greater MPO activity in cell-free BAL and lung homogenates were observed when compared with the saline control group （P〈0.01）. There was a significant increase in lung ICAM-1 mRNA in response to LPS challenge （P〈0. 01, group L versus group S）. Genistein pretreatment significantly attenuated LPS-induced changes in these indices. LPS caused extensive lung damage, which was also lessened after genistein pretreatment. All above-mentioned parameters in the genistein alone group were not significantly different from those of the saline control group. It is concluded that genistein pretreatment attenuated LPS-induced lung injury in rats. This beneficial effect of genistein may involves, in part, an inhibition of neutrophilic recruitment and activity, possibly through an inhibition of lung ICAM-1 expression.     

重型颅脑损伤致急性肺损伤发病机制的实验研究

目的从炎性因子角度探讨重型颅脑损伤单一因素致继发肺损伤的机制。方法参照第三军医大学大坪医院野战外科研究所第四研究室建立的气动冲击致重型颅脑损伤模型,将22只雄性SD大鼠按随机数字表法分为正常组（n=4）和损伤组（n=18）。损伤组在伤后1、3、7d各处死6只动物进行观察。用光镜、电镜观察肺组织形态学改变;放射免疫法监测支气管肺泡灌洗液（BALF）中TNF-α和IL-8水平;酶联免疫吸附实验测定BALF中可溶性细胞间黏附分子-1（sICAM-1）的水平。结果光镜下损伤组大鼠各时相均可见肺毛细血管充血、炎性细胞渗出及肺泡间隔增宽等病理改变。3d时肺组织的病理改变评分显著高于1、7d（P〈0.01）。电镜显示,损伤组在各时相均可见血管内皮细胞肿胀,毛细血管充血、炎性细胞渗出,肺泡上皮细胞损伤等改变,以3d时最为显著。BALF中TNF-α、IL-8、sICAM-1水平在各时相点均明显高于正常组（P〈0.01）,3d时达到峰值（P〈0.01）;相关分析显示,病理改变评分与TNF-α、IL-8水平正相关（r=0.920,0.867,P〈0.01）,与sICAM-1水平呈中度正相关（r=0.555,P〈0.05）。结论重型颅脑损伤大鼠在伤后1～7d均出现显著的肺损伤,3d时损伤最显著。肺损伤的发生与重型颅脑损伤后肺局部分泌过多的TNF-α、IL-8、sICAM-1等炎性因子有关。     

微小RNA在急性肺损伤中的研究进展

急性肺损伤是由各种直接或间接因素导致肺泡上皮细胞及毛细血管内皮细胞损伤,造成弥漫性肺间质和肺泡水肿,进而导致急性低氧性呼吸功能不全.微小RNA(microRNA,miRNA)与急性肺损伤的发生、发展关系密切,在肺泡上皮细胞、毛细血管内皮细胞及巨噬细胞等细胞的分化、增殖、凋亡、分解过程及对信号通路的调节中发挥重要作用.因...     

重症急性胰腺炎合并肺损伤的发生机制研究进展

重症急性胰腺炎(sever acute pancreatitis,SAP)在起病初期,即有由细胞因子介导的全身炎症反应综合征(systematic inflammatory response syndrome,SIRS)引起的多器官功能衰竭(multiple organ dysfunction failure,MOF).SIRS和MOF是危及患者生命的主要并发症,其特点是多器官功能不全,其中急性肺功能不全合并MOF是最常见的、也是发病率最高的胰腺外器官.临床上表现为急性呼吸窘迫症,病情危急,严重危及生命.因此,研究SAP并发MOF的机制可为SAP治疗提高理论基础,本文就近年来国内外有关SAP合并急性肺损伤的机制进行综述.     

体外膜肺氧合对急性肺损伤治疗的实验研究

目的 探讨体外膜肺氧合(ECMO)对内毒素(LPS)诱导大鼠急性肺损伤(aLI)的治疗效果.方法 LPS静脉注射复制大鼠急性肺损伤模型.40只健康雄性SD大鼠随机分为4组:LPS组(L组:静脉注射LPS)、对照组(C组:静脉注射生理盐水)、机械通气治疗组(LV组:ALI模型制备成功后,行机械通气2h)、ECMO治疗组(LE组:ALI模型制备成功后,行机械通气及ECMO治疗2h),每组10只.实验结束时,将4组大鼠在无菌条件下开胸取出两肺,取左肺下叶同一部位小块肺组织,测定肺湿/干质量比值;取右肺下叶同一部位两小块组织,分别用于HE染色观察肺组织的病理改变及作TUNEL法观察细胞凋亡数.结果 与C组比较,L组的肺组织湿/干质量比值增加(P<0.01);与L组比较,LV组、LE组的肺组织湿/干质量比值减少(P<0.05);LV组和LE组的肺组织湿/干质量比值差异无显著性(P>0.05).与C组比较,L组、LV组与LE组的肺组织凋亡指数升高(P<0.01);与L组比较,LE组的凋亡指数下降(P<0.05),L组和LV组的肺组织凋亡指数差异无显著性(P>0.05);与LV组比较,LE组的凋亡指数下降(P<0.05).凋亡指数分级为:C组0级,L组3级,LV组3级,LE组2级.光镜下观察发现L组的肺组织损伤及细胞凋亡程度最为严重,LV组次之,而LE组较LV组减轻.结论 体外膜肺氧合对内毒素诱导大鼠急性肺损伤有治疗作用.     

Pathogenesis of acute lung injury in severe acute pancreatitis

Objective：To study the pathogenesis of acute lung injury in severe acute pancreatitis （SAP）. Methods：Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results： After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion：There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.     

硫化氢调节急性肺损伤大鼠肺泡上皮细胞凋亡

Background Acute lung injury (ALI) is a common syndrome associated with high morbidity and mortality in emergency. Cell apoptosis plays a key role in the pathogenesis of ALI. Hydrogen sulfide (H2S) plays a protective role during acute lung injury. We designed this study to examine the role of H2S in the lung alveolar epithelial cell apoptosis in rats with acute lung injury. Methods Sixty-nine male Sprague Dawley rats were used. ALI was induced by intra-tail vein injection of oleic acid (OA). NaHS solution was injected intraperitonally 30 min before OA injection as NaHS pretreatment group. Single sodium hydrosulfide pretreatment group and control group were designed. Index of quantitative assessment (IQA) and the percentage of polymorphonuclear leucocyte (PMN) cells in the bronchoalveolar lavage fluid (BALF) were calculated. H2S level in lung tissue was measured by sensitive sulphur electrode. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Fas protein was measured by immunohistochemical staining. Results The level of endogenous H2S in lung tissue decreased in the development of ALI induced by OA injection. Apoptosis and Fas protein in alveolar epithelial cells increased in ALI of rats but NaHS lessened apoptosis and Fas protein expression in alveolar epithelial cells of rats with ALI. Conclusion Endogenous H2S protects rats from oleic acid-induced acute lung injury probably by inhibiting cell apoptosis.