红景天苷对脂多糖所致急性肺损伤治疗作用的研究

目的:观察红景天苷（SDS）对脂多糖（LPS）引起的大鼠急性肺损伤（ALI）的治疗作用,并初步探讨其作用的机制。方法: 将36只SD大鼠随机分为生理盐水（NS）对照组、LPS组和LPS+SDS组(每组n=12),通过向气管内滴注LPS建立大鼠ALP模型。采用微量注射泵向大鼠右颈外静脉注射液体并留置的给药方法,NS组和LPS组注射NS并留置4 h;LPS+SDS组先于气管内滴注LPS,0.5 h后再注射SDS并留置4 h。4.5 h后处死实验动物,取肺组织观察其形态学改变,测定肺湿/干质量的比值（W/D）、肺泡灌洗液（BALF）中蛋白的含量及肺组织匀浆中TNF-α、IL-6、IL-10、乳酸脱氢酶(LDH)和髓过氧化物酶(MPO)的含量。结果: 形态学观察表明,LPS组肺组织水肿,有点、片状出血及大量的炎性细胞浸润,肺泡间隔显著增厚,肺泡腔变窄、结构消失。LPS+SDS组的肺组织损伤明显减轻,肺组织结构趋于正常,肺泡腔及支气管腔炎细胞及渗出物与LPS组相比明显减少。LPS组肺W/D与NS组相比明显增加（P<0.05）,BALF中蛋白的含量显著增加（P<0.05）,肺组织匀浆中TNF-α、IL-6、IL-10、LDH和MPO的含量显著增加（P<0.05）;而给予SDS治疗后,肺W/D、BALF中蛋白含量、肺组织匀浆中TNF-α、IL-6、LDH和MPO的含量与LPS组相比均明显减少（P<0.05）,IL-10含量显著增加（P<0.05）。结论: SDS对LPS所致ALI具有治疗作用,这种治疗作用可能与其通过抑制肺组织中炎症介质的作用有关。     

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.     

银杏叶总黄酮对脂多糖所致小鼠急性肺损伤的保护作用

目的 探讨银杏叶总黄酮对急性肺损伤(aute lung injury,ALI)的防治作用及其作用机制.方法 50只雄性ICR小鼠随机分为正常对照组、ALI模型组和银杏叶总黄酮(total ginkgo flavone glycosides,TFG)低、中、高剂量组,每组10只,采用脂多糖(lipopolysaccharide,LPS)诱导小鼠ALI模型,给药后测定小鼠肺湿/干重比,伊文斯蓝法检测肺血管通透性,检测肺组织匀浆中超氧化物歧化酶(superoxide dismutase,SOD)活力和丙二醛(malondialdehyde,MDA)含量,观察各组肺组织的病理变化,免疫组织化学染色技术检测肺组织中核因子κB(nuclear factor-kappaB,NF-κB)的表达.结果 与ALI模型组相比,TFG高剂量组可降低升高的肺湿/干重比(P＜0.05),降低肺血管的通透性;与ALI模型组比较,TFG组肺组织匀浆中SOD活力升高、MDA含量下降(P值均＜0.01);HE染色显示ALI模型组气道管腔内有大量炎性细胞聚集,肺泡内有大量蛋白水肿液,TFG各给药组病变较ALI模型组减轻;ALI模型组NF-κB表达显著增加(P＜0.01),TFG治疗组则明显减少.结论 TFG对LPS所致ALI小鼠有明显的保护作用,其机制可能与其提高抗氧化能力,阻断NF-κB的表达有关.     

大承气汤对脂多糖所致老年大鼠急性肺损伤的作用

目的 探讨大承气汤(DD)在脂多糖(LPS)所致老年大鼠急性肺损伤(ALI)中的作用.方法 将140只SD老年大鼠随机分为对照组、LPS组(经气管内滴注LPS复制ALI模型)、DD+LPS组和DD组.各组大鼠于给药后4或8 h处死,测定肺系数;光镜观察肺组织形态学改变;化学法检测肺组织丙二醛(MDA)含量以及支气管肺泡灌洗液(BALF)的中性粒细胞(PMN)数目和蛋白含量的变化.各组再取7只动物,右心导管法监测并记录给药前及给药后2、4、6、8 h时的平均肺动脉压(mPAP).结果 气管内滴注LPS可引起mPAP明显升高(P＜0.01),肺组织明显的形态学改变;肺系数和肺组织MDA含量增加(P＜0.01);BALF中PMN数目和蛋白含量增加(P＜0.01).给予DD后,mPAP明显降低,肺组织损伤减轻,肺系数和肺组织MDA含量下降(P＜0.05),BALF中PMN数目和蛋白含量减少(P＜0.01). 结论 DD具有抗LPS所致老年大鼠ALI的作用.     

G-CSF对老年大鼠急性肺损伤过程中脂质过氧化及HO-1表达的影响

目的探讨粒细胞集落刺激因子(G-CSF)处理对肺组织形态学、脂质过氧化及HO-1表达的影响。方法 60只SD老年大鼠随机分为假手术组、ALI组和G-CSF组,每组20只,采用气管内滴入脂多糖(LPS)方法诱导大鼠急性肺损伤模型。G-CSF于模型建立成功后给药后12 h处死动物,测定肺系数;光镜观察肺组织形态学改变;化学比色法检测肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性;RT-PCR方法检测肺组织血红素氧合酶-1(HO-1)mRNA表达的变化。结果与假手术组相比,ALI组肺组织形态学明显改变,肺系数及肺组织MDA含量增加,SOD活性下降,HO-1表达减少;与ALI组相比,G-CSF组大鼠肺组织损伤减轻,肺系数和肺组织MDA含量下降,SOD活性增加,HO-1表达增加。结论 G-CSF可以显著增加SOD活性和HO-1表达,减少MDA生成,从而在ALI过程中对肺组织起到保护作用。     

Resolvin D1对脂多糖诱导小鼠急性肺损伤的保护作用

目的 探讨Resolvin D1（RvD1）对脂多糖（LPS）诱导小鼠急性肺损伤的治疗作用。方法体重20~25 g的BALB/c小鼠21只随机分3组,1对照组,气管内滴注PBS;2LPS模型组,气管内滴注LPS（100μg/60μl）,作用6 h;3RvD1组,在气管内滴注LPS 30 min前给予RvD1（600 ng/100μl/只）尾静脉注射,LPS作用6小时。观察各组小鼠肺组织病理组织学变化,肺泡灌洗液（BALF）中炎症细胞总数及中性粒细胞变化,BALF中促炎性细胞因子IL-6及抗炎性细胞因子IL-10含量变化及肺组织内丙二醛（MDA）的浓度。结果 在LPS刺激的小鼠中,组织病理学显示大量的炎性细胞浸润,肺泡内出血,水肿,肺组织结构明显被破坏,BALF中细胞总数、中性粒细胞及肺组织内MDA含量明显增高,BALF中促炎性细胞因子IL-6显著升高。而以RvD1预处理小鼠明显抑制LPS诱发的上述改变,同时中抗炎因子IL-10显著升高。结论 RvD1可能通过重建抗炎反应和炎症反应的平衡对急性肺损伤发挥保护作用。     

人脐带间充质干细胞对ALI治疗作用的研究

目的探讨输入人脐带间充质干细胞（human umbilical cord mesenchymal stem cells,HUMscs）对脂多糖（LPS）诱导的大鼠ALI的治疗作用。方法将30只Wistar大鼠随机分为3组：正常对照组、ALI模型组和HUMSCs移植组,每组10只。健康大鼠LPS气管滴入方法建立ALI模型,尾静脉输入HUMSCs。输入7h后,处死各组大鼠,取肺组织行病理学观察,测定肺湿／干重比（W／D）,ELISA法测定肺组织匀浆中肿瘤坏死因子α（TNF-α）和IL-1β的含量。结果肺组织病理学显示：ALI模型组大鼠肺组织呈现典型的炎症病理变化,包括肺泡充血、水肿、出血,肺泡腔和血管壁中性粒细胞浸润,肺泡壁增厚等肺损伤性病变;HUMSCs移植组大鼠肺组织损伤程度明显减轻。与正常对照组比较,ALI模型组W／D、TNF-α和IL-1β含量明显升高（P〈0．05）。与Au模型组比较,HUMSCs移植组W／D、TNF-α和IL-1β含量明显降低（P〈0．05）。结论输入HUMSCs能减轻ALI,并能降低肺W／D和肺组织TNF-α及IL-1β含量。     

TNF-α中和对脂多糖致急性肺损伤小鼠肺组织凋亡的影响

目的 评价TNFR-Fc通过下调炎症反应、抑制组织细胞凋亡,对脂多糖(LPS)致急性肺损伤(ALI)小鼠肺组织的保护性作用.方法小鼠随机分为LPS组、TNFR-Fc+ LPS组和对照组.气管内滴人LPS复制ALI小鼠模型,TNFR-Fc+ LPS组在滴人LPS前24 h腹膜腔注射TNFR-Fc 0.4mg/kg体质量,在滴入LPS后2h收集标本.ELISA法检测血清肿瘤坏死因子α(TNF-α)及支气管肺泡灌洗液(BALF)中TNF-α、白介素1β(IL-1β)与IL-6浓度,BCA法检测BALF中蛋白含量,qRT-PCR法检测Bax基因转录强度,末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法检测肺组织细胞凋亡率,组织病理半定量评分评价肺组织损伤程度.结果 LPS气管内滴入后,BALF中TNF-α、IL-6浓度与肺泡蛋白含量显著升高(P＜0.05),肺组织Bax基因转录强度均显著增高(P＜0.05),给予TNFR-Fc预处理显著降低血清TNF-α浓度,BALF中IL-6浓度与蛋白含量也显著下降(P＜0.05),下调Bax基因的转录强度(P＜0.05).与LPS组相比,TNFR-Fc+ LPS组小鼠肺组织细胞凋亡率、病理评分均显著降低(P＜0.05).结论 中和TNF-α能下调肺局部炎症反应强度,减少LPS致ALI小鼠肺组织细胞凋亡,降低LPS气管内滴人引起的肺组织损伤程度.     

硫化氢在脂多糖所致老年大鼠急性肺损伤中的作用

目的 探讨硫化氢(H2S)在脂多糖(LPS)所致老年大鼠急性肺损伤(ALI)中的作用机制.方法 64只SD老年大鼠随机分为对照组、LPS组、NaHS+LPS组、炔丙基甘氨酸(PPG)+LPS组,每组16只.LPS组、NaHS+LPS组、PPG+LPS组经气管内滴注LPS 200 μg/只,制备大鼠ALI模型;对照组经气管内滴注无菌生理盐水200 μl/只.NaHS+LPS组制模前10 min腹腔注射NaHS 28 μmol/kg,PPG+LPS组制模前10 min腹腔注射PPG 45 mg/kg.给药后4 h或8 h处死动物,测定肺系数;光镜观察肺组织形态学改变;化学法检测血浆H2S、NO和CO含量、肺组织丙二醛(MDA)含量、胱硫醚-γ-裂解酶(CSE)、诱导型一氧化氮合酶(iNOS)和血红素加氧酶-1(HO-1)活性;采用免疫组织化学法检测肺组织iNOS、HO-1蛋白表达及吸光度值.结果 气管内滴注LPS可引起肺组织明显的形态学改变;肺系数和肺组织MDA含量增加;血浆H2S含量和肺组织CSE活性下降;肺组织iNOS活性和iNOS蛋白表达增强,血浆NO含量增加;肺组织HO活性和HO-1蛋白表达增强,血浆CO含量增加.预先给予NaHS可显著减轻LPS所致肺组织损伤,肺系数和肺组织MDA含量下降;血浆H2S含量和肺组织CSE活性升高;肺组织iNOS活性和iNOS蛋白表达减弱,血浆NO含量减少;肺组织HO活性和HO-1蛋白表达增强,血浆CO含量增加(均P＜0.05).而预先给予PPG可加重LPS所致肺损伤,使血浆NO含量、肺组织iNOS活性和iNOS蛋白表达进一步增加(均P＜0.05),但对血浆CO含量、HO活性和HO-1蛋白表达无明显影响.结论 H2S/CSE体系的下调在LPS所致老年大鼠ALI的发病学中有一定作用,而外源性给予一定量的NaHS对肺组织具有保护作用,其可能与抗氧化效应和下调NO/iNOS体系、上调CO/HO-1体系有一定关系.     

全反式维甲酸对肺气肿大鼠氧化应激的影响

目的观察全反式维甲酸（ATRA）对猪胰蛋白酶（PPE）致大鼠肺气肿模型的氧化应激的影响。方法选60只Wistar大鼠随机分为对照组（N）和模型组（E）,棉籽油组（C）,小剂量ATRA治疗组（L）,中剂量ATRA治疗组（M）,大剂量AT-RA治疗组（H）各10只为研究对象,用大、中、小剂量ATRA和棉籽油注入大鼠腹腔内进行治疗。30天后处死解剖大鼠,测量大鼠肺体积,肺泡形态学,肺组织SOD活力和MDA含量。结果 E、C、L、M、H组大鼠肺体积,肺泡形态学,氧化应激水平均明显大于N组（P〈0.05）;L组肺组织SOD活力较E组显著增高;L、M组肺组织MDA含量较E组显著降低（P〈0.05）。结论肺气肿模型大鼠用低剂量ATRA治疗对肺泡有较好修复作用,可提高肺组织SOD活力,降低肺组织MDA含量,可以起到抗氧化保护肺组织作用。     

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.     

Effects of intratracheal tumor necrosis factor-alpha plasmid vector on lipopolysaccharide lethality and lung injury in mice

Bacterial lipopolysaccharide (LPS) causes acute lung injury (ALI) and contributes to inflammation in the acute respiratory distress syndrome (ARDS) and sepsis, making mechanisms of resistance to LPS critically important in clinical settings. The authors postulated that intratracheal administration of a plasmid (pcDNA3. 0-rTNFalpha) encoding rat tumor necrosis factor-alpha (TNF-alpha) would increase resistance of mice to LPS-induced ALI or mortality. They investigated the time course and dose-response for development of LPS-induced ALI in C57/BL6 mice and sought possible protective effects of 100 microg pcDNA3.0-rTNFalpha intratracheally 1, 2, or 3 weeks before LPS challenge. Lung myeloperoxidase (MPO) activity and alveolar lavage fluid (BALF) cell counts increased significantly 48 hours after intraperitoneal (IP) LPS challenges. After pcDNA3.0-rTNFalpha pretreatment, mice challenged with LPS had lower lung/body weight ratios than mice treated with pcDNA3.0; however, other indices of lung injury did not differ. Survival of mice challenged with lethal IP LPS 2 weeks after intratracheal pcDNA3.0-rTNFalpha vector improved significantly, compared to mice pretreated with the control vector, pcDNA3.0. However, pcDNA3.0-pretreated mice tolerated LPS challenge less well than saline-pretreated controls. LPS causes neutrophilic lung injury and mortality, but pcDNA3.0-TNFalpha does not prevent ALI due to LPS. Intratracheal pcDNA3.0-rTNFalpha pretreatment significantly improves survival of mice after LPS challenge, compared to those pretreated with pcDNA3.0.     

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。     

Evaluation of lung injury and respiratory mechanics in a rat model of acute pancreatitis complicated with endotoxin

BackgroundAcute lung injury (ALI) is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths, particularly in the setting of secondary infection. This ‘two-hit’ model mimics clinical cases where the presentation of AP is associated with mild lung injury that, following a secondary direct lung infection, can result in respiratory dysfunction and death. We therefore aimed to characterize lung injury in a clinically-relevant ‘two-hit’ rat model of caerulein-induced AP combined with intratracheal endotoxin.MethodsRats received 7 hourly intraperitoneal injections of caerulein (50 μg/kg). Twenty four hours following the first caerulein injection, rats were anaesthetised and LPS (15 mg/kg) was instilled intratracheally. Following LPS instillation, rats were ventilated for a total of 2 h.ResultsIn the present study, AP results in mild pulmonary injury indicated by increased lung myeloperoxidase (MPO) activity and edema, but with no alteration of respiratory function, while intratracheal instillation of LPS results in more substantial pulmonary injury. The induction of AP challenged with secondary intratracheal LPS results in an exacerbation of lung damage indicated by further increased lung edema, plasma and bronchoalveolar (BAL) CINC-1 concentration, lung damage histology score, and lung tissue resistance and elastance, compared with LPS alone.ConclusionsIn conclusion, the addition of instilled LPS acted as a “second-hit” and exacerbated caerulein-induced AP, compared with the induction of AP alone or the instillation of LPS alone. Given its clinical relevance, this model could prove useful for examination of therapeutic interventions for ALI following secondary infection.     

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     

一氧化碳吸入对急性肺损伤大鼠肺组织细胞凋亡的影响及其机制

目的观察吸入低浓度一氧化碳(CO)对脂多糖(LPS)致急性肺损伤(ALI)大鼠肺组织细胞凋亡的影响,探讨可能机制。方法18只雄性SD大鼠随机均分为3组。ALI组静脉滴注LPS5mg/kg,正常对照组注入生理盐水,CO吸入组在LPS诱导肺损伤后持续吸入体积分数为2.5×10-4CO。观察3h后放血处死,取肺组织,半定量逆转录聚合酶链反应(RT PCR)测定血红素氧化酶1(HO1)表达,酶联免疫吸附测定(ELISA)法检测肿瘤坏死因子α(TNFα)、白细胞介素6(IL6)和IL10的含量;化学比色法测定丙二醛(MDA)含量、髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)活性;光镜观察并盲法评分比较肺组织学;流式细胞仪检测细胞凋亡。结果ALI组HO1mRNA、TNFα、IL6、IL10、MDA、MPO、SOD、细胞凋亡与正常对照组[1.002±0.004、(0.47±0.06)pg/mg蛋白、(0.49±0.12)pg/mg蛋白、(0.42±0.08)pg/mg蛋白、(0.79±0.14)nmol/mg蛋白、(6.0±1.0)U/mg蛋白、(74±7)U/mg蛋白、(0.12±0.03)%]比较差异均有统计学意义(P<0.05或<0.01),肺损伤严重。CO吸入组TNFα、IL6、MDA、MPO和细胞凋亡[(0.91±0.25)pg/mg蛋白、(0.64±0.05)pg/mg蛋白、(1.02±0.23)nmol/mg蛋白、(7.2±1.6)U/mg蛋白、(1.60±0.34)%]显著低于ALI组[(1.48±0.23)pg/mg蛋白、(1.16±0.26)pg/mg蛋白、(1.27±0.33)nmol/mg蛋白、(8.2±1.5)U/mg蛋白、(3.18±0.51)%,P均<0.05];HO1mRNA、IL10和SOD表达[5.433±0.921、(0.26±0.07)pg/mg蛋白、(60±10)U/mg蛋白]显著高于ALI组[3.081±0.823、(0.15±0.03)pg/mg蛋白、(51±7)U/mg蛋白,P均<0.05],肺损伤减轻。结论吸入CO通过调控氧化/抗氧化、促炎/抗炎反应、抑制过度细胞凋亡和上调HO1表达,可能对LPS诱导ALI起保护作用。     

Insulin reduces LPS-induced lethality and lung injury in rats

Insulin is a main glucose homeostatic hormone in the body. Previous reports showed that insulin also exerted anti-inflammatory actions and attenuated systemic inflammatory response. Here, we observed the effects and the underlying mechanisms of insulin on lipopolysaccharide (LPS)-induced acute lung injury (ALI). As revealed by survival study, insulin reduced mortality of rats and prolonged their survival time. Meanwhile, insulin significantly reduced the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in bronchoalveolar lavage fluid (BALF). Besides, insulin markedly inhibited the expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB). Taken together, these data provided information that insulin attenuated LPS-induced ALI may attribute partly to the inhibition of the production of cytokines, and the expression of TLR2, TLR4 and NF-κB.     

Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury

RATIONALE: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. OBJECTIVE: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. METHODS: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. MEASUREMENTS AND MAIN RESULTS: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. CONCLUSIONS: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.