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。     

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。     

Low-dose dexamethasone alleviates lipopolysaccharide-induced acute lung injury in rats and upregulates pulmonary glucocorticoid receptors

Background and objective: The major causes of mortality among patients who survive acute lung injury/ARDS (ALI/ARDS) are due to the extensive tissue remodelling and fibrosis. Use of high‐dose glucocorticoids to reduce these inflammatory and fibroproliferative responses has been shown to do more harm than good. Recently, Meduri et al. found that the early use of low‐dose prolonged methylprednisolone in patients with severe ALI/ARDS significantly relieved the systemic inflammatory response and improved pulmonary and extrapulmonary organ function. This study investigated the therapeutic effect of low‐dose dexamethasone (Dex) on inflammation and fibrosis in LPS‐induced ALI in rats and its influence on the expression of the pulmonary glucocorticoid receptor (GR). Methods: Eighty Wistar rats were randomly divided into four groups: a control group (intraperitoneal normal saline injection (5 mL/kg) throughout experiment, n = 24); the LPS model group (LPS injection (5 mg/kg) for 3 days and normal saline thereafter, n = 24); the LPS + Dex group (LPS injection for 3 days and Dex solution (5 mg/kg) thereafter, n = 16); and the Dex group (normal saline injection (5 mL/kg) for 3 days and Dex solution (5 mg/kg) thereafter, n = 16). Levels of tumor necrosis factor‐α, matrix metallopeptidase‐9 and procollagen N‐terminal propeptide type I in BAL fluid were examined by ELISA on the third, seventh and fourteenth days after injection. Pulmonary hydroxyproline content was measured and histological examination was performed with haematoxylin–eosin and Victoria blue‐ponceau. Pulmonary distribution of GR‐positive cells was examined immunohistochemically, and expression of GR mRNA and protein was determined by RT‐PCR and western blot analysis. Results: Histological assessments showed that pulmonary fibrosis occurred in parallel with inflammation in the rat ALI model. Compared with the LPS group, the inflammation and fibrosis parameters were significantly improved in the LPS + Dex group at different periods after injection (P < 0.05 or P < 0.01), although parameters in the LPS + Dex group were not as good as those of the control group. GR mRNA and protein expression in the LPS + Dex group were markedly higher than that of the LPS group on the seventh and the fourteenth days (both P < 0.01). Western blotting showed that Dex also promoted the nuclear translocation of GR protein. Conclusion: Low‐dose Dex can reduce pulmonary inflammation and fibrosis after LPS‐induced ALI in rats and can elevate GR expression in the lung, probably through upregulating GR levels and promoting the nuclear translocation of GR protein.     

Comparing the protective effects of ciprofloxacin, moxifloxacin and levofloxacin in mice with lipopolysaccharide-induced acute lung injuries

Background and objective:   Ciprofloxacin, moxifloxacin and levofloxacin are recognized immunomodulators. Their effects in acute lung injuries have not been tested. This study compared the immunoprotective effects of these agents in mice with lung injuries induced by LPS by measuring the cytokine profiles in the injured lung and the associated mortality.
Methods:   The development of lung injury and mortality was compared in mice pretreated with either ciprofloxacin, levofloxacin, moxifloxacin or saline (control group) after the intratracheal administration of LPS. BALF and serum were collected at 1, 3 and 6 h to measure the concentrations of tumour necrosis factor-α (TNF-α), IL-1β, IL-6, IL-10 and macrophage inflammatory protein-2 (MIP-2) using enzyme-linked immunoassay.
Results:   Levels of TNF-α, IL-1β and MIP-2 in the BAL of the ciprofloxacin group were significantly lower compared with those of controls (all P  < 0.0083) at 3 and 6 h after LPS challenge. There were no significant differences in the levels of these cytokines in the moxifloxacin and levofloxacin groups compared with controls. Overall, the 96-h survival for the mice pretreated with ciprofloxacin, but not for those pretreated with moxifloxacin or levofloxacin, was significantly greater than that of the control animals ( P  = 0.019).
Conclusions:   In the setting of LPS-induced lung injuries, ciprofloxacin appears to provide better anti-inflammatory properties and survival benefits than the other fluoroquinolones tested.     

The pathogenesis of transfusion-related acute lung injury (TRALI)

In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.     

急性肺损伤大鼠肺纤维增生早期检测

目的探讨油酸（OA）所致大鼠急性肺损伤（ALI）早期肺纤维组织增生情况及其可能的纤维化机制。方法应用尾静脉注射OA复制大鼠ALI模型。48只健康SD大鼠（体质量0．29～0．31kg，雌雄不拘）随机分为4组：生理盐水对照组（NS组，n=12），OA致伤1d组（OA1组，n=12），OA致伤3d组（OA2组，n=12），OA致伤7d组（0A3组，n=12）。OA致伤组以0．12ml／kg的OA尾静脉注射，NS组注射同等量的生理盐水。观察肺部病理变化，检测肺湿／干重比（W／D值），测定动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、pH值及血浆Ⅲ型前胶原肽N末端（PⅢNP）浓度，测支气管肺泡灌洗液（BALF）中总蛋白（TP）、总磷脂（TPL）、磷脂酰胆碱（PC）和PⅢNP浓度。结果①与NS组比较，OA组肺组织可见明显充血、水肿、出血等ALI表现，各时间点BALF中TPL、PC／TPL明显减少（P〈0．01），而TP、W／D值、PⅢNP及血浆PⅢNP显著升高（P〈0．01），动脉血PaO2、PaCO2、pH值也有明显变化（P〈0．01）。②OA组各时间点血浆与BALF中PmNP浓度呈正相关（rOA1=0．864，P〈0．01；rOA2=0．829，P〈0．01；rOA3=0．874，P〈0．01）。结论AU早期肺就发生纤维组织增生；ALI时PⅢNP浓度显著升高，通过检测BALF和血浆中的PⅢNP浓度可能有助于早期诊治ALI.     

依布硒啉对急性肺损伤大鼠氧化应激的影响

目的 观察依布硒啉对内毒素性急性肺损伤的保护作用.方法 健康雄性SD大鼠,随机分成6组:正常对照组、模型组、依布硒啉高剂量组、中剂量组、低剂量组和地塞米松对照组.通过尾静脉注射LPS(5 mg/kg)建立模型,治疗组于造模前30 min,大鼠腹腔注射依布硒啉(7.5 mg/kg、15 mg/kg、30 mg/kg),对照组和模型组分别注入等量溶剂.造模后6h,麻醉放血处死动物,并取肺组织,测定肺湿质量/干质量.采用硫代巴比妥酸和黄嘌呤氧化法分别检测肺组织中超氧化物歧化酶SOD活性和丙二醛MDA及髓过氧化物酶(MPO)含量.光镜下观察肺组织病理学改变.结果 依布硒啉治疗组与模型组相比,肺湿质量/干质量降低,肺组织SOD的活性明显增高,MDA和MPO含量显著降低(P＜0.05),病理改善明显.结论 依布硒啉对内毒素性急性肺损伤有一定保护作用,其机制可能与提高抗氧化能力有关.     

The role of neutrophils in the pathogenesis of obliterative bronchiolitis after lung transplantation

Abstract: Obliterative bronchiolitis (OB) represents the most important long-term complication after lung transplantation. Elevated numbers of neutrophils within the airways are a hallmark of OB. It is unclear what causes the recruitment and activation of neutrophils in the airways of patients with OB: the process of chronic rejection itself or infection, which may (especially in latent virus infection) often be overlooked by the currently applied diagnostic procedures. It is well known that besides their physiologic functions in the clearance of invading micro-organisms, activated neutrophils have a remarkable potential to cause damage to lung tissue. This is attributable to their capability to generate reactive oxygen species and to release potentially toxic proteases. It has been shown that the increased numbers of neutrophils in bronchoalveolar lavage fluid of patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation are associated with elevated levels of interleukin-8, the predominant neutrophil chemotactic factor in the lung. As evidence for the impact of neutrophils on the pathogenesis of BOS, there is significant oxidative stress within the airways of patients with BOS. In addition, the milieu within the airways is characterized by an imbalance between neutrophil elastase (NE) and molecules that inhibit NE as a result of an increased burden of NE released by neutrophils. A defective antiprotease shield due to the loss of secretory leukoprotease inhibitor could be demonstrated in BOS. These mechanisms may provide possible targets to develop new therapeutic strategies that either prevent neutrophil sequestration and activation, or inhibit neutrophil products in order to prevent or attenuate airway damage.     

以ALI为表现的脓毒症患者外周血PBMC TLR4 mRNA及IL-34、IL-36的表达

目的观察以ALI为表现的脓毒症患者外周血PBMC TLR4 mRNA及IL-34、IL-36的表达及与该病的相关性,探讨其对以ALI为表现的脓毒症诊断的敏感度与特异度。方法以ALI为表现的脓毒症住院患者38例为ALI组,正常体检者30例为对照组。收集研究d1及d7血液标本,应用Real Time PCR测定外周血单个核细胞(PBMC)的TLR4 mRNA,应用ELISA法检测IL-34、IL-36。结果 d7 ALI组外周血PBMC TLR4mRNA及IL-34、IL-36含量均明显低于相同患者治疗前水平(P均0.001),治疗前ALI外周血PBMC TLR4mRNA及IL-34、IL-36含量均明显高于对照组(P均0.001)。相关分析表明,IL-34浓度均与外周血PBMC TLR4 mRNA及IL-36浓度呈正相关(r=0.5746及0.968,P0.05),IL-36浓度与外周血PBMC TLR4 mRNA浓度不相关(r=-0.0679)。脓毒症患者治疗前血清中上述细胞因子的ROC曲线下面积(AUC)分别为0.932、0.957和0.901。外周血PBMC TLR4 mRNA取949、IL-34取88.10ng/ml、IL-36取1.03ng/ml为截断值,诊断以ALI为表现的脓毒症敏感性均为100%,特异性为0.73%、77%及84%。结论以ALI为表现的脓毒症患者外周血PBMC TLR4 mRNA及IL-34、IL-36的含量与疾病发生发展关系密切,通过监测上述细胞因子的含量可以对脓毒症病情诊断及评估做出一定的判断。     

BALF对周围型肺癌的诊断价值

目的探讨支气管肺泡灌洗液(BALF)对内镜检查阴性的周围型肺癌患者的诊断价值。方法选取我科2011年1月至2014年7月住院行支气管镜检查镜下阴性的患者共114例,进行支气管肺泡灌洗和支气管镜下肺活检(TBLB)。根据病理结果 ,将所有患者分为肺癌(周围型肺癌)组和肺良性病变组。对比两组患者BALF中肿瘤指标水平和细胞基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)、Survivin mRNA相对表达量。以开胸手术或经皮肺穿刺病理活检结果为金标准,对比IBAL和TBLB检测对于肺癌的灵敏度、特异度。结果肺癌组BALF中CEA、CYFRA21-1、ET-1和NSE水平显著高于肺良性病变组,P0.01。肺癌组的MMP-7、Survivin mRNA相对表达量显著高于肺良性病变组,P0.01。IBAL检测肺癌的灵敏度为72.41%,特异度为62,50%;TBLB检测肺癌的灵敏度为79.31%,特异度为67.86%。两种检测肺癌方法灵敏度和特异度无显著差异,P0.05。结论行支气管肺泡灌洗可以提高内镜检查阴性周围型肺癌患者的诊断率,进而早期手术治疗。     

内毒素导致的急性肺损伤治疗的研究进展

急性肺损伤(ALI)可迅速发展为急性呼吸窘迫综合征(ARDS),内毒素血症是ALI最主要的原因之一,治疗效果不理想,病死率高,一直是临床和基础研究关注的焦点。近年来在抗炎、抗氧化、抗凝治疗等方面进行了大量的实验研究,但尚缺乏临床试验的验证。目前作为治疗ALI/ARDS的主要方法——呼吸机治疗在通气模式的研究方面进展较快...     

纤维支气管镜下肺泡灌洗治疗重型颅脑损伤并肺部感染的疗效分析

目的探讨纤支镜下支气管肺泡灌洗治疗重型颅脑损伤并肺部感染的疗效。方法将72例重型颅脑损伤并肺部感染随机分为治疗组36例、对照组36例。对照组予以抗生素、营养支持、雾化吸入、经鼻导管吸痰等综合治疗,治疗组在综合治疗基础上经纤支镜下肺泡灌洗。对两组患者临床症状、体征、外周血白细胞计数、痰菌培养、有效率及治疗前后血气分析结果进行分析。结果治疗组体温恢复正常,痰液明显减少或消失,肺部哕音明显减少或消失,外周血白细胞计数正常,痰菌转阴时间均明显短于对照组（P〈0．01）,治疗组临床总有效率明显优于对照组（94．45％vs86．11％,P〈0．05）,纤支镜组治疗后血气改善明显（P〈0．001）。结论纤支镜下支气管肺泡灌洗是一种安全有效的治疗重型颅脑损伤并肺部感染方法。     

IL-8及SPB蛋白在兔海水及淡水淹溺型急性肺损伤模型中的表达

目的探究组织白细胞介素(IL-8)及表面活性蛋白B(SPB)在兔海水及淡水淹溺型急性肺损伤模型中的表达。方法选取实验中心饲养健康成年新西兰兔36只,采用随机数表分组,将其分海水组,淡水组与对照组。三组兔均在动物房饲养一周后行麻醉下气管插管,气管插管完成后,海水组兔经气管插管向气管内注射3 mL/kg配置海水,淡水组经气管插管向气管内注射18 mL/kg配置淡水,对照组兔仅行麻醉气管插管操作。手术操作完成后,持续插管通气4 h,通气结束后处死各组实验兔,收集肺组织,光学显微镜下观察各组兔肺组织病理学改变情况,测定肺组织干湿重比(W/D);比较三组兔肺泡灌注液中IL-8及SPB蛋白表达情况;比较三组兔肺组织IL-8及SPB蛋白表达情况。结果海水组与淡水组W/D较对照组均明显上升,结果具有统计学意义(P<0.05),且两组兔肺组织W/D无明显差异(P>0.05);海水组与淡水组肺泡灌洗液中IL-8水平较对照组表达均上升,SPB蛋白较对照组明显下降,结果具有统计学意义(P<0.05),且两组兔肺泡灌洗液中IL-8及SPB蛋白水平无明显差异(P>0.05);海水组与淡水组肺组织中IL-8水平较对照组表达均上升,SPB水平较对照组明显下降(P<0.05),且两组兔肺组织中IL-8及SPB蛋白表达无明显差异(P>0.05)。结论海水组及淡水组淹溺型急性肺损伤实验兔肺泡灌洗液及肺组织IL-8水平均明显上升,SPB水平均明显下降,提示IL-8表达增多及SPB蛋白表达下调与该损伤发生过程密切相关。     

Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice

Abstract:  Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.     

Fatal idiopathic acute eosinophilic pneumonia with acute lung injury

A fatal case of idiopathic eosinophilic pneumonia with acute lung injury is described. The patient required treatment with mechanical ventilation and intravenous corticosteroids, however, she died on the third hospital day. At autopsy, both exudative and proliferative phases of diffuse alveolar damage were observed bilaterally. Marked eosinophilic infiltrate was noted in the alveolar wall and within the alveolar cavities with occasional abscess-like features. To our knowledge, this is the first report of fatal acute eosinophilic pneumonia, and provides important information for the management of this condition.     

支气管肺泡灌洗在严重肺部感染中的治疗作用

目的探讨支气管肺泡灌洗(BAL)对严重肺部感染的临床疗效。方法对65例原发或继发严重肺部感染病例,进行随机对照研究,32例给予常规治疗(对照组);33例在正常治疗的基础上加用BAL治疗(BAL组)。分别于治疗后3、7及14d判断临床疗效以及评估BAL治疗时的并发症和不良反应。结论对照组在治疗后3、7、14 d显效率分别为34.4%、40.6%、43.8%,BAL组显效率分别为51.5%、66.7%、69.7%,两组间疗效差异有显著性(P<0.01)。BAL治疗组无1例严重并发症。结论BAL治疗严重肺部感染疗效显著,安全可靠,简便易行,值得临床推广。     

Transfusion‐related acute lung injury after intravenous immunoglobulin treatment in a lung transplant recipient

Three weeks after single‐lung transplantation for pulmonary fibrosis, a patient with high serum levels of de novo donor‐specific antibodies received high‐dose intravenous immunoglobulin (IVIG) infusion (scheduled dose: 2 g/kg on 2 days) to prevent antibody‐mediated rejection. Within the first hours after completion of infusions, he experienced acute lung injury involving the transplanted lung. Given the clinical evolution and the absence of an alternative diagnosis, transfusion‐related acute lung injury (TRALI) was diagnosed. The IVIG administered on each day was from the same batch. At day 110, because of an increase in the serum titers of donor‐specific antibodies, IVIG therapy was reintroduced but from a different batch, with excellent clinical tolerance. The lung injury was explored biologically, but no mechanism was revealed. Given the increasing use of IVIG in solid‐organ recipients, clinicians should be aware of possible TRALI after IVIG infusion.