肥胖小鼠急性肺损伤模型的生物学特点

目的探讨LPS诱导的肥胖小鼠急性肺损伤模型的生物学特点。方法按照处理方式的不同分为四组:NC/NS组、NC/LPS组、DIO/NS组、DIO/LPS组,采用LPS腹腔注射的方法诱导小鼠急性肺损伤的动物模型。记录生存时间,计算不同实验组的生存率;观察各实验组中急性肺损伤各指标(肺组织病理学变化、湿干比、髓过氧化物酶活性、支气管肺泡灌洗液中炎症因子表达)。结果肥胖组与正常组小鼠急性肺损伤模型生存率无显著差异;肥胖组小鼠急性肺损伤模型肺组织病理学评分、湿干比、髓过氧化物酶活性较正常小鼠显著升高;肥胖组小鼠急性肺损伤模型支气管肺泡灌洗液中IL-10表达水平较正常小鼠显著降低,但TNF-α表达水平无显著差异。结论肥胖组小鼠炎症反应水平较正常小鼠显著升高,这可能与抗炎细胞因子IL-10水平降低有关。     

内毒素致大鼠急性肺损伤模型的建立

目的建立经尾静脉注射脂多糖致大鼠急性肺损伤动物模型。方法大鼠尾静脉注射5 mg/kg脂多糖,造成急性肺损伤,于注射脂多糖2 h后,分别测定动脉血气分析、血清蛋白含量、肺泡灌洗液中蛋白、细胞间粘附分子-1的含量、肿瘤坏死因子-α、白介素-8,计算肺湿/干重比、肺通透指数,观察肺组织病理学改变。实验设置生理盐水对照组。结果肺组织病理切片提示脂多糖组肺间质大量炎性细胞浸润,出血、水肿,而生理盐水组肺组织损伤轻微。对照组肺湿/干重比、肺泡通透指数、肺泡灌洗液中中性粒细胞比均显著低于脂多糖组(P<0.05),而动脉血氧分压则高于脂多糖组(P<0.05)。脂多糖组肺泡灌洗液中肿瘤坏死因子-α、细胞间粘附分子-1、白介素-8浓度高于对照组(P<0.05)。结论此模型基本符合急性肺损伤诊断标准及动物模型的考察指标符合临床,说明本模型是成功可靠的。     

抵抗素样分子-α在急性胰腺炎继发急性肺损伤中的表达和作用

背景:抵抗素样分子-α(RELM-α)是一个富含半胱氨酸的分泌蛋白,具有促进肺血管生成和收缩、抗细胞凋亡、诱导肺成纤维细胞分化和细胞外基质沉积的功能。然而,RELM-α在急性胰腺炎(AP)继发急性肺损伤中的作用尚未完全明确。目的:探讨RELM-α在AP继发急性肺损伤中的表达和作用。方法:45只Sprague-Dawley大鼠随机分为急性坏死性胰腺炎(ANP)组、急性水肿性胰腺炎(AEP)组和正常对照组,分别以3.5%牛磺胆酸钠和20%L-精氨酸建立ANP和AEP模型。光学显微镜下观察肺组织病理学表现;测定肺湿/干重系数、支气管肺泡灌洗液炎性细胞数量以及血清CRP、淀粉酶水平;蛋白质印迹法和免疫组化法检测肺组织RELM-α的表达和定位。结果:ANP组肺组织病理学评分、肺湿/干重系数、支气管肺泡灌洗液炎性细胞数量、血清CRP和淀粉酶水平、肺组织RELM-α表达水平均较AEP组和正常对照组显著升高(P0.05)。Spearman等级相关系数分析显示,肺组织RELM-α表达水平与肺组织病理学评分、肺湿/干重系数、支气管肺泡灌洗液炎性细胞数量呈正相关(P0.01)。线性回归模型分析显示,肺组织RELM-α表达水平与血清CRP、淀粉酶水平呈正相关(P0.05)。结论:RELM-α在AP急性肺损伤的肺组织中表达增高,其作为促炎细胞因子,参与激活炎性细胞,介导急性肺损伤发生,可作为监测AP预后的生物学标记物。     

PIAS1对重症急性胰腺炎继发急性肺损伤血气屏障影响的研究

背景:研究发现STAT活化抑制蛋白1(PIAS1)可抑制急性坏死性胰腺炎(ANP)继发急性肺损伤,但机制尚不明确。目的:探讨PIAS1对ANP大鼠继发急性肺损伤血气屏障的作用及其机制。方法:构建重组腺病毒Ad5/F35-PIAS1和Ad5/F35-Null质粒。以3.5%牛磺胆酸钠胰胆管逆行注射诱导大鼠ANP模型,并于造模前1 d分别经阴茎静脉注射Ad5/F35-PIAS1、Ad5/F35-Null和PBS液,设立假手术组作为对照。造模16 h后处死大鼠。观察胰腺和肺组织的病理学变化和超微结构改变。测定支气管肺泡灌洗液炎性细胞计数和肺组织湿/干重系数,以免疫组化法检测RECK定位表达,蛋白质印迹法检测肺组织RECK、MMP-2、MMP-9、ICAM-1蛋白表达。结果:与ANP组和Ad5/F35-Null组相比,Ad5/F35-PIAS1组胰腺和肺组织病理学明显改善,肺组织病理学评分显著降低(P<0.01),超微结构示肺泡毛细血管间血气屏障结构破坏减轻;支气管肺泡灌洗液中性粒细胞和巨噬细胞计数、湿/干重系数均显著降低(P<0.01);肺组织RECK蛋白表达显著升高(P<0.01),MMP-2、MMP-9、ICAM-1蛋白表达显著下调(P<0.01);Ad5/F35-PIAS1组上述指标与对照组相比均无明显差异(P>0.05)。结论:PIAS1可能通过增强RECK蛋白表达、抑制MMP-2、MMP-9、ICAM-1蛋白表达,降低血气屏障通透性,抑制炎性细胞外渗,进而改善ANP继发急性肺损伤的炎症程度。     

鹿茸草对脂多糖诱导的大鼠 ALI 的保护作用研究

目的：探讨鹿茸草对脂多糖(LPS)诱导的大鼠 ALI 的保护作用。方法健康成年雄性 SD 大鼠60只随机分为4组：对照组、鹿茸草组、LPS 组、LPS+鹿茸草组,每组15只。LPS 诱导肺损伤前30 min,鹿茸草水煎液0.2 g/ml 和生理盐水分别自胃内注射到大鼠体内。大鼠 ALI 通过气管滴注 LPS (3 mg/kg)诱导。2 h 后麻醉处死大鼠,评估肺损伤情况。结果预先给予鹿茸草,可使肺泡出血和炎性损伤表现相对减轻,肺组织湿干重比值明显降低。此外,鹿茸草显著抑制炎症因子 IL-1β和肿瘤坏死因子α的表达水平以及细胞凋亡指数。结论鹿茸草对 LPS 诱导的大鼠 ALI 具有肺保护作用。     

乙酰化白藜芦醇对脂多糖诱导急性肺损伤中微循环修复作用机制探究

目的观察脂多糖(LPS)诱导急性肺损伤大鼠肺组织中微循环的变化,探讨乙酰化白藜芦醇对其干预作用及机制。方法 32只SD大鼠随机分为空白对照组、LPS处理组、乙酰化白藜芦醇预处理组和白藜芦醇预处理组,每组8只。采用气管内滴注LPS(5 mg/kg)的方法制作急性肺损伤动物模型,观察病理变化、肺组织湿/干重比值,用伊文思蓝法检测肺微血管通透性,用酶联免疫吸附试验法检测肺组织中肿瘤坏死因子α和白细胞介素1β的含量,用蛋白质印迹法检测细胞骨架重构相关蛋白FAK、cofilin的表达变化,免疫荧光观察肺微血管内皮细胞单层细胞间隙改变情况。结果 LPS干预4 h后,大鼠肺部损伤明显,肿瘤坏死因子α和白细胞介素1β的含量增高,肺湿/干重比值及通透性明显增加,FAK-cofilin通路明显激活,肺微血管内皮单层细胞间隙明显增加;乙酰化白藜芦醇预处理显著减轻了LPS导致的急性肺损伤,减少了炎症因子的释放,并且抑制了FAK-cofilin通路的激活及肺微血管内皮单层细胞间隙的增加。结论肺微循环的改变参与了LPS诱导肺损伤的发生发展,乙酰化白藜芦醇能够通过抑制FAK-cofilin通路减轻肺损伤。     

不同急性肺损伤大鼠模型Na^＋-K^＋-ATP酶活性变化及对地塞米松的反应

目的 探讨肺泡上皮细胞膜上Na^ -K^ -ATP酶在盐酸(HCI)和脂多糖(LPS)两种原因致急性肺损伤大鼠肺水生成中的作用及地塞米松(Dex)治疗肺水肿的意义。方法96只雄性SD大鼠随机分为6组(每组16只)：生理盐水对照组(NS组)、NS Dex组、Hcl模型组、HCl Dex组、LPS模型组、LPS Dex组，每组又分为支气管肺泡灌洗(BAL)亚组和非支气管肺泡灌洗(NBAL)亚组。NBAL组观察肺组织病理改变、湿干重比(W／D)、Na^ -K^ -ATP酶水解活性和哇巴因与其受体Na^ -K^ -ATP酶特异性结合位点数量的变化；BAL组观察支气管肺泡灌洗液(BALF)中细胞数及蛋白含量的变化。结果①两种模型组Na^ -K^ -ATP酶水解活性和酶位点数在激素干预前均显著低于干预后水平。并且显著低于对照组水平。②激素干预前两种模型组BALF中细胞总数、PMN分类计数、蛋白含量显著高于干预后水平，显著低于对照组水平。结论Na^ -K^ -ATP酶在肺水的转运中起重要作用，ALI时肺泡膜上Na^ -K^ -ATP酶的活性降低可能是产生肺水肿的重要机制之一，地塞米松可以分别增加两种模型组Na^ -K^ -ATP酶水解活性和位点数；地塞米松可以减轻LPS组肺水肿(以W／D表示)的程度，但对HCl组无效。     

普拉格雷对海水吸入型急性肺损伤的作用分析

目的探讨海水吸入型急性肺损伤中血小板与中性粒细胞的黏附情况,以及普拉格雷对其的干预作用。 方法SD大鼠随机分为海水吸入1、2 h两个大组,组内随机分为空白对照组、海水处理组、溶剂处理组与普拉格雷处理组,每组8只大鼠。海水处理组在大鼠气管内灌注海水,溶剂处理组和普拉格雷处理组在海水处理之前4 h分别给予羟甲基纤维素钠溶液(CMC-Na)和普拉格雷灌胃处理。分别进行各组的病理切片HE染色,检测各组肺组织湿干比、血浆中炎症因子浓度,流式细胞术下检测血小板活化率以及与中性粒细胞的黏附情况,并进行肺泡灌洗液蛋白浓度测定以及髓过氧化物酶(MPO)活性测定。 结果与正常对照组比较,气管内滴入海水后大鼠肺部组织出现明显炎症和水肿,HE染色显示其组织结构紊乱,肺泡间质充血水肿,并有大量炎症细胞浸润,肺泡间隔明显增厚,ELISA法测得全身炎症因子,如TNF-α、IL-1β以及TXB2的表达增高,血小板与中性粒细胞黏附率显著增加,肺泡灌洗液蛋白定量以及MPO活性增加,并且海水吸入2 h较1 h各项指标增高更为显著。普拉格雷干预可显著减轻海水导致的肺组织损伤,减轻肺组织结构紊乱与炎症细胞浸润,减少炎症因子TNF-α、IL-1β以及TXB2的释放,并且抑制血小板的活化以及与中性粒细胞的黏附。 结论海水吸入型急性肺损伤中血小板与中性粒细胞的黏附率明显升高,普拉格雷可能通过降低此指标对肺损伤产生保护作用。     

RIP3介导的程序性坏死通路在LPS诱导的小鼠急性肺损伤模型中的作用

目的研究受体相互作用蛋白(RIP3)介导的程序性坏死通路在脂多糖(LPS)诱导的小鼠急性肺损伤模型(ALI)中的作用。方法将野生小鼠和RIP3敲除小鼠各30只分为四组:(a)Control RIP3-KO,(b)LPS RIP3-KO,(c)Control RIP3-WT,(d)LPS RIP3-WT。每组各15只,脂多糖组(LPS组)经小鼠气管套管滴入30mg/kg LPS,对照组经气管套管滴入等体积磷酸盐缓冲液(PBS),然后观察比较四组小鼠肺部病理损伤,小鼠直肠温度和生存率,并检测小鼠肺组织冰冻切片中坏死细胞计数和肺泡灌洗液中高迁移率族蛋白B1(HMGB1)水平。结果 RIP3敲除后,小鼠肺部病理损伤减轻,低体温症状得到明显改善,且死亡率降低。冰冻切片显示的肺组织坏死细胞计数减少,且支气管肺泡灌洗液中HMGB1表达水平也降低。结论 RIP3敲除能一定程度保护小鼠免受LPS诱导的急性肺损伤,并能减少肺组织细胞坏死的发生。     

葛根芩连汤对内毒素诱导的急性肺损伤小鼠的保护机制

目的探讨葛根芩连汤对内毒素(LPS)诱导小鼠急性肺损伤(ALI)的保护作用。方法小鼠腹腔注射LPS(5 mg/kg)复制ALI动物模型。将小鼠随机分为空白对照组、LPS组、地塞米松组(2 mg/kg)、葛根芩连汤低剂量组(6.5 g/kg)、葛根芩连汤高剂量组(13 g/kg)。观察各组肺组织病理学改变,测量肺湿/干重比、丙二醛(MDA)、炎症因子白介素(IL)-6、肿瘤坏死因子(TNF)-α含量及肺组织中Toll样受体(TLR2)、TLR4与核因子(NF)-κB P65蛋白表达。结果葛根芩连汤可有效减轻LPS所致肺组织病理学变化,能降低肺泡灌洗液中炎症细胞的数目,能显著降低肺湿/干重比重并能降低减低TLR2、TLR4与NF-κB P65蛋白。结论葛根芩连汤可减轻LPS所致ALI,对LPS诱导的核因子有保护作用。     

Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation.

Intercellular adhesion molecule-1 (ICAM-1) is known to play a central role in lung inflammation. Limited information, however, is available regarding the expression and biological function of ICAM-1 in the alveolar epithelial compartment. The current report analyses the expression pattern of ICAM-1 in primary cultures of rat alveolar epithelial cells (AECs) and in the rat lung following instillation of bacterial endotoxin (lipopolysaccharide (LPS)) in order to better define the role of alveolar epithelial ICAM-1. AECs stimulated in vitro with LPS were evaluated for ICAM-1 and ICAM-1 messenger ribonucleic acid content. Adherence assays with neutrophils and macrophages were performed. Endotoxin-induced ICAM-1 upregulation on AECs was demonstrated in vivo by immunofluorescence staining. In addition, the effect of intratracheally-instilled anti-ICAM-1 was assessed. Significant upregulation of ICAM-1 occurred in vitro and in vivo on AECs after LPS stimulation. Adherence assays showed a 114% increase in adhesion of neutrophils to AECs. Antibody directed against ICAM-1 reduced this adhesion by 40%. A significant reduction in the number of neutrophils in bronchoalveolar lavage fluid and whole lung was seen under airway ICAM-1 blockade. These data indicate that intercellular adhesion molecule-1 participates in the inflammatory response to lipopolysaccharide-induced lung injury in the distal airways by interacting mainly with neutrophils.     

内毒素急性肺损伤 TLR4-LPS 信号传导对 NF-κB 活性的影响黄继义简

目的 本文旨通过检测肺组织TLR4、NF-κB表达及支气管肺泡灌洗液炎症因子含量,探讨TLR4/NF-Kb信号在ALI发病中的作用.方法 30只大鼠随机分为对照组、ALI组和干预组.静脉注射LPS构建肺损伤模型,实时定量PCR及western blot检测肺组织TLR4、NF-κB表达,ELISA法检测TNF-α、IL-1β浓度.结果 肺损伤评分：ALI组〉TLR4拮抗剂干预组〉对照组,肺泡灌洗液TNF-α、IL-1β浓度较对照组分别增加了7倍和3.5倍.ALI组肺组织中TLR4和NF-κB表达明显增加,TLR4拮抗剂能抑制二者表达.结论 TLR4/NF-κB信号通路在脂多糖大鼠急性肺损伤模型的发展过程中起重要作用,TLR-4受体过表达诱导NF-κB活化及其下游炎症因子释放,加重急性肺损伤.     

Contributions of high mobility group box protein in experimental and clinical acute lung injury

This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.     

Importance of tumor necrosis factor-alpha cleavage process in post-transplantation lung injury in rats

Tumor necrosis factor-alpha (TNF-alpha) has two forms with apparently different biological activities: a membrane-associated form and a soluble form. TNF-alpha-converting enzyme (TACE) mediates a cleavage of membrane-associated TNF-alpha to induce its bioactive soluble form. We hypothesized that inhibition of TACE might prevent TNF-alpha-induced tissue injury while preserving the benefits of TNF-alpha. In this study, we evaluated the role of TACE in acute inflammation using an inhibitor of the enzyme in a rat model of lung transplantation. Inbred Lewis rats underwent left lung isotransplantation, and the donor lungs were kept in Euro-Collins solution with or without the inhibitor. After 6 hours of ischemia, the left lung was transplanted into the recipient rat and reperfused for 4 hours. Inhibition of TACE significantly attenuated endothelial and alveolar septal damage, as assessed by radiolabeled albumin leakage after transplantation. The inhibition also attenuated neutrophil accumulation in the alveolar space and other histopathologic findings, including intercellular adhesion molecule-1 expression. In addition, significantly lower levels of monocyte chemotactic protein-1, cytokine-induced neutrophil chemoattractant-1, high mobility group box-1, and soluble epithelial cadherin and decreased neutrophil elastase activity were observed in bronchoalveolar lavage fluid from the rats treated with the inhibitor. We conclude that TACE mediates a critical step in the development of post-transplantation lung injury.     

Resolution of acute lung injury and inflammation: a translational mouse model

Previous animal models of acute lung injury (ALI) are limited as they only reproduce part of the complex pathobiology of clinical ALI. Here we develop a translational mouse model of ALI, which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution. Anaesthetised mice underwent orotracheal instillation of hydrochloric acid. During the immediate period after instillation, mice were carefully maintained with supplemental oxygen to avoid mortality. At specified time-points, lung injury was assessed by analysis of blood gases, respiratory mechanics, bronchoalveolar lavage fluid, alveolar fluid clearance and lung histology. Animals exhibited significant weight loss, decreased oxygenation, increased respiratory elastance and pulmonary inflammation (intra-alveolar leukocyte influx/cytokine levels and histological injury scores). Moreover, mice displayed alveolar-capillary barrier dysfunction/epithelial injury as reflected by increased alveolar protein, lung wet/dry weight ratio and soluble receptor for advanced glycation end-products, as well as reduced alveolar fluid clearance. These injury parameters peaked between days 1 and 3, followed by almost complete recovery over days 5-10. Histology showed evidence of fibrosis on day 10. The results indicate that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALI.     

银杏叶提取物对脂多糖诱导D-半乳糖致衰老大鼠急性肺损伤的保护作用

目的　观察脂多糖 (LPS)诱导D 半乳糖 (D gal)致衰老大鼠急性肺损伤 (ALI)及银杏叶提取物 (GBE)对其是否有保护作用。方法　大鼠 2 4只随机分成两部分 ,6只为正常对照组 ;18只经腹腔注D gal复制衰老动物模型。后者再随机分成三组 :衰老对照组 (6只 ) ;LPS组 (6只 ,静脉注射LPS诱导形成ALI) ;GBE +LPS组 (6只 ,注LPS前 7天开始每天灌胃给GBE一次 ,按所含黄酮甙计算 ,8mg/kg体重 ,实验当日在给LPS前 2h再给一次GBE)。注LPS后 2h收集标本待测。结果　D gal致衰老大鼠较正常大鼠血中超氧化物歧化酶 (SOD)及肺组织Na+ K+ ATPase活性均显著降低 (P均 <0 0 5 ) ,而血中乳酸脱氢酶 (LDH)活性升高 (P <0 0 5 )。衰老大鼠注LPS后 2h已形成ALI。肺间质及肺泡中有较多炎性细胞 ;肺泡灌洗液中蛋白含量及肺通透指数增加 ;血中乳酸 (LD) ,丙二醛 (MDA) ,一氧化氮 (NO) ,内皮素 1(ET 1) ,肿瘤坏死因子 α(TNF α)含量和LDH活性以及肺组织中髓过氧化物酶 (MPO)活性 ,均显著升高 ;而血中超氧化物歧化酶活性及肺组织Na+ K+ ATPase活性均下降 (P <0 0 5 ,P <0 0 1)。预先给予GBE可显著地缓解除SOD活性外的上述其它指标的变化 (P <0 0 5 )。结论　D gal致衰老大鼠体内抗氧化能力降低。静注LPS可引起衰老大鼠明显的A     

Opposite effects of ANP receptors in attenuation of LPS-induced endothelial permeability and lung injury

Atrial natriuretic peptide (ANP) has been recently identified as a modulator of acute lung injury (ALI) induced by pro-inflammatory agonists. While previous studies tested effects of exogenous ANP administration, the role of endogenous ANP in the course of ALI remains unexplored. This study examined regulation of ANP and its receptors NPR-A, NPR-B and NPR-C by LPS and involvement of ANP receptors in the modulation of LPS-induced lung injury. Primary cultures of human pulmonary endothelial cells (EC) were used in the in vitro tests. Expression of ANP and its receptors was determined by quantitative RT-PCR analysis. Agonist-induced cytoskeletal remodeling was evaluated by immunofluorescence staining, and EC barrier function was characterized by measurements of transendothelial electrical resistance. In the murine model of ALI, LPS-induced lung injury was assessed by measurements of protein concentration and cell count in bronchoalveolar lavage fluid (BAL). LPS stimulation significantly increased mRNA expression levels of ANP and NPR-A in pulmonary EC. Pharmacological inhibition of NPR-A augmented LPS-induced EC permeability and blocked barrier protective effects of exogenous ANP on LPS-induced intercellular gap formation. In contrast, pharmacological inhibition of ANP clearance receptor NPR-C significantly attenuated LPS-induced barrier disruptive effects. Administration of NPR-A inhibitor in vivo exacerbated LPS-induced lung injury, whereas inhibition of NPR-C suppressed LPS-induced increases in BAL cell count and protein content. These results demonstrate for the first time opposite effects of NPR-A and NPR-C in the modulation of ALI and suggest a compensatory protective mechanism of endogenous ANP in the maintenance of lung vascular permeability in ALI.     

重组人促红细胞生成素对内毒素诱导的ALI/ARDS大鼠的干预作用

目的：观察重组人促红细胞生成素(rhEPO)对 ALI/ARDS大鼠模型肺部炎症及肺-毛细血管通透性的干预。方法24只雌性 SD大鼠随机分为正常对照组、ALI/ARDS组、EPO 低剂量组和 EPO 高剂量组。以腹腔注射内毒素进行造模,不同剂量的 rhEPO 进行干预。末次干预后收集BALF计数炎症细胞以及蛋白总量;计量肺湿/干重比;HE染色观察肺组织病理变化。结果与正常对照组比较,ALI/ARDS组肺组织病理损害严重,肺湿/干重比增加,BALF中白细胞总数、中性粒细胞、淋巴细胞以及蛋白总量均显著增加(P 值均<0.01);与 ALI/ARDS 组比较,EPO 低剂量组和EPO 高剂量组肺组织病理损害明显缓解,肺湿/干重比下降,BALF 中白细胞总数、中性粒细胞、淋巴细胞以及蛋白总量均显著下降(P值均<0.01),且 EPO 高剂量组效果优于 EPO 低剂量组(P <0.05或P<0.01)。结论 rhEPO 可以明显改善ALI/ARDS大鼠肺组织炎症水平,降低肺-毛细血管通透性,有效抑制 ALI/ARDS的发病进程。     

气体信号分子硫化氢对大鼠急性肺损伤的保护作用

目的 观察急性肺损伤(acute lung injury,ALI)时,内源性硫化氢(hydrogen sulfide,H2S)生成的变化以及应用外源性H2S后对ALI的影响.方法 Sprague-Dawley大鼠随机分为对照组、脂多糖(lipopolysaccharide,LPS)组、硫氢化钠(sodium hydrosulfide,NaHS)+LPS组以及NaHS+生理盐水(normal saline,NS)组(n均=12).LPS组大鼠每只气管内滴注LPS(100 μg/200 μl),对照组滴注等量NS.NaHS+LPS组大鼠滴注LPS前10 min腹腔注射NaHS(28 μmol/kg).各组均于滴注后4 h和8 h测定大鼠肺系数变化,光镜下观察肺组织形态学改变,检测肺组织中氧化性损伤产物丙二醛(malondialdehyde,MDA)含量以及支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中蛋白含量及中性粒细胞(polymorphonuclear neutrophil,PMN)计数的改变,并测定血浆中的H2S含量.结果 与对照组相比,LPS滴注4 h和8 h后,大鼠肺系数、肺组织中MDA含量、BALF中PMN数目及蛋白含量均明显升高(P值均＜0.01);而血浆中H2S含量则明显降低(P值均＜0.01);光镜下见肺泡萎陷、甚至结构消失,肺泡腔及间质弥漫性炎细胞浸润,部分肺泡代偿性气肿,且其病理改变随LPS滴注时间的延长而逐渐加重.与相应时间点的LPS组比较.NaHS+LPS组大鼠肺系数、肺组织中MDA含量、BALF中PMN数目及蛋白含量明显降低,血浆中H2S含量则明显升高(P值均＜0.01);光镜下肺间质和肺泡中炎细胞浸润程度明显减轻.结论 内源性H2S生成不足参与了ALI的形成过程,外源性H2S可以部分拮抗ALI,对肺组织起到细胞保护作用.