IL-27 is Elevated in Acute Lung Injury and Mediates Inflammation

Cytokines play a critical role in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here we investigated whether IL-27 was elevated in patients with ALI/ARDS and its potential clinical significance. Bronchoalveolar lavage (BAL) and serum samples were obtained from 58 ALI/ARDS patients, and 25 control healthy volunteers. IL-27 and other inflammatory mediators were measured in BAL and serum by ELISA. Besides, a mouse model of cecal ligation and puncture (CLP)-induced lung inflammation/injury was established, and serum, BAL fluid and tissues were collected for analyses in the presence or absence of IL-27 neutralizing antibodies. BAL IL-27 was found to be significantly higher in patients with ALI/ARDS than that in controls, particularly of pulmonary origin; serum IL-27 was also significantly higher. Increased IL-27 was associated with markers of inflammation, and correlated with disease severity of patients in ALI/ARDS. In a mouse model of CLP-induced lung inflammation/injury, elevated IL-27 levels were observed in the lung, serum, and BAL fluids. IL-27 neutralizing antibody treatment reduced pulmonary inflammation and lung injury and improved mouse survival in response to CLP. Therefore, IL-27 is a critical cytokine in ALI/ARDS and inhibition of IL-27 may open a promising approach for ALI/ARDS patients.     

TNFR-Fc减轻LPS所致小鼠ALI炎症反应损伤

目的: 评价肿瘤坏死因子受体-Fc融合蛋白(TNFR-Fc)能否有效下调炎症反应而减轻急性肺损伤(ALI)小鼠的肺组织破坏。方法: 小鼠随机分为脂多糖(LPS)组、TNFR-Fc+LPS组和对照组。气管内滴入LPS复制ALI小鼠模型,TNFR-Fc组在滴入LPS前24 h腹膜腔注射TNFR-Fc (0.4 mg/kg),在滴入LPS后2 h收集标本,检测肺湿/干重、肺泡蛋白含量与肺组织病理评分;ELISA法检测血清TNF-α浓度及检测肺泡灌洗液与血清IL-1β、IL-6、IL-10与IFN-γ浓度。结果: TNFR-Fc显著降低血清TNF-α浓度(P＜0.05),轻度降低肺湿/干重比例,显著降低BALF蛋白浓度(P＜0.05),显著降低ALI评分数值(P＜0.05)。TNFR-Fc显著降低致炎症细胞因子IL-6在BALF(P＜0.05)与血清(P＜0.05)中的浓度,轻度提高BALF中IL-10浓度(P＞0.05),但其差异不显著,亦能显著提高血清IL-10浓度(P＜0.05)。IL-1β与IFN-γ水平处理前后变化不显著。结论: TNFR-Fc中和ALI中过度表达的TNF-α,下调以IL-6为代表的炎症反应,减轻ALI的肺组织破坏。     

全身炎症反应综合征-肺损伤大鼠肺组织IL-10mRNA表达及AP-1活性变化的研究

目的:复制脂多糖(LPS)致伤大鼠的全身炎症反应综合征(SIRS)-肺损伤模型,检测肺组织IL-10mRNA含量和AP-1活性的改变,探讨抗炎机制在SIRS-肺损伤中的作用。方法:梯级剂量LPS致伤Wistar大鼠,复制SIRS-肺损伤模型;逆转录PCR法(RT-PCR)检测大鼠肺组织IL-10mRNA含量;凝胶迁移率分析法(EMSA)检测大鼠肺组织激活蛋白-1(AP-1)活性。结果:①LPS致伤大鼠,可以模拟SIRS-肺损伤发生;②LPS≥6mg/kg可以导致ARDS形成,类似SIRS失控表现;③LPS可以导致大鼠肺组织IL-10mRNA含量和AP-1活性升高;④在非失控性演进为失控性SIRS-肺损伤过程中,当LPS≥6mg/kg时,大鼠肺组织IL-10mRNA含量和AP-1活性的升高幅度最大。结论:①LPS≥6mg/kg是大鼠SIRS-肺损伤发生失控的临界剂量;②大鼠SIRS-肺损伤失控伴有IL-10基因转录及其调控的异常增强;③抗炎机制增强参与了SIRS-肺损伤发生、发展的病理生理过程。     

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury <Emphasis Type="Italic">via</Emphasis> NF-κB Signaling Pathway <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.     

NPS 2143, a selective calcium-sensing receptor antagonist inhibits lipopolysaccharide-induced pulmonary inflammation

NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF). NPS 2143 also reduced the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, NPS 2143 attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased the activation of AMP-activated protein kinase (AMPK) in the lung. NPS 2143 also downregulated the activation of nuclear factor-kappa B (NF-κB) in the lung. In LPS-stimulated H292 airway epithelial cells, NPS 2143 attenuated the releases of IL-6 and MCP-1. Furthermore, NPS 2143 upregulated the activation of AMPK and downregulated the activation of NF-κB. These results suggest that NPS 2143 could be potential agent for the treatment of inflammatory diseases including ALI.     

Protective Effect of p-Cymene on Lipopolysaccharide-Induced Acute Lung Injury in Mice

In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor alpha (TNF-α), IL-1β, and IL-6 were assayed by enzyme-linked immunosorbent assay method. The pathological changes of the lung tissues were observed by hematoxylin and eosin staining. The inflammatory signal pathway-related protein levels of NF-κB were measured using Western blotting. The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice.     

Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation

Artesunate, a derivative of artemisinin, has been reported to have anti-inflammatory property. However, few studies showed the protective effects of artesunate on lung injury. In this study, we aimed to investigate the effects of artesunate on LPS-induced lung injury in mice. The mice were treated with artesunate 1 h before or after LPS treatment. The effects of artesunate on lung MPO activity and malondialdehyde (MDA) content were detected. The lung wet/dry radio and the numbers of inflammatory cells in BALF were also measured. ELISA was used to evaluate the levels of TNF-α, IL-1β, and IL-6 in BALF. Western blot analysis was adapted to detect TLR4 and Nrf2 signaling pathways. The results showed that artesunate protected against LPS-induced ALI by decreasing the numbers of inflammatory cells, lung edema, MPO activity, and MDA content. Furthermore, artesunate significantly inhibited the levels of TNF-α, IL-1β, and IL-6. Artesunate also inhibited LPS-induced IL-6 and IL-8 production in the A549 cells. In addition, artesunate dose-dependently suppressed LPS-induced TLR4 expression and NF-κB activation. The expression of Nrf2 and HO-1 were also up-regulated by artesunate. The data suggest that artesunate possesses anti-inflammatory and anti-oxidant properties against LPS-induced ALI via inhibiting TLR4 signaling pathway and activating Nrf2 signaling pathway.     

p38 MAPK-HSP27信号通路在内毒素致大鼠肺损伤中的作用

 目的：观察p38丝裂原激活蛋白激酶（p38 MAPK)-热休克蛋白27（HSP27）信号通路在急性肺损伤病理过程中的变化规律。方法：健康雄性Wistar大鼠（300~320 g）随机分成正常对照组（A组）、急性肺损伤组（B组）及急性肺损伤+SB203580组（C组）。通过腹腔注射内毒素建立急性肺损伤大鼠模型,分别于实验开始后的0、2、4、6、8 h处死各组大鼠。检测支气管肺泡灌洗液（BALF）白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）及BALF中蛋白含量。苏木素-伊红（HE）染色检查肺组织病理变化及免疫荧光方法检测内皮细胞内F-actin和G-actin,计算肺湿干重比值（W/D）。检测肺组织中磷酸化p38 MAPK（p-p38 MAPK）及磷酸化HSP27（p-HSP27）的含量。 结果：B组在实验后2 h BALF中蛋白水平和肺W/D开始明显增加,给予内毒素后8 h肺泡上皮肿胀,肺泡壁增宽,肺泡间质和肺泡腔水肿明显,肺泡内炎症细胞、红细胞和蛋白渗出明显增多,表现出急性肺损伤的病理改变。在给予了p38 MAPK抑制剂SB203580后的C组BALF中蛋白水平及肺W/D分别比B组明显减少,肺泡内炎症细胞、红细胞和蛋白渗出、间质与肺泡水肿均较B组减轻。B组均在实验后2 h血清及BALF中TNF-α和IL-6的浓度开始增加,p-p38 MAPK及p-HSP27的肺内表达开始增加,与A组相比有显著差异。B组实验后8 h的F-actin的表达明显比A组实验后0 h及8 h的增加,给予p38 MAPK抑制剂SB203580的C组肺p-HSP27 和F-actin的表达分别比B组明显减少。结论：内毒素可以通过激活p38 MAPK-HSP27信号通路引起急性肺损伤;阻断该信号通路可以减轻肺损伤。     

Mining the acute respiratory distress syndrome proteome: identification of the insulin-like growth factor (IGF)/IGF-binding protein-3 pathway in acute lung injury

To obtain a more complete protein profile of the airspace milieu in acute respiratory distress syndrome (ARDS) and to identify new mediators, we analyzed bronchoalveolar lavage fluid (BALF) by shotgun proteomics. Using BALF from three patients, we identified a total of 870 different proteins, a nearly 10-fold increase from previous reports. Among the proteins identified were known markers of lung injury, such as surfactant, proteases, and serum proteins. We also identified several biologically interesting proteins not previously identified in patients with ARDS, including insulin-like growth factor-binding protein-3 (IGFBP-3). Because of the known role of IGFBP-3 in regulating cell survival, we measured IGFBP-3 levels by enzyme-linked immunosorbent assay in ARDS BALF. Normal controls had low levels of IGFBP-3, whereas patients with early ARDS had a significant increase in IGFBP-3. The IGF pathway, acting through the type 1 IGF-receptor, repressed apoptosis of lung fibroblasts but not lung epithelial cells. Furthermore, depletion of IGF in ARDS BALF led to enhanced fibroblast apoptosis. Our data suggest that the IGFBP-3/IGF pathway is involved in the pathogenesis of lung injury, illustrating the power of shotgun proteomics to catalog proteins present in complex biological fluids, such as BALF, from which hypotheses can be developed and tested.     

大承气汤治疗大鼠内毒素性ARDS的疗效分析及免疫调节机制研究

目的： 探讨大承气汤对内毒素“二次打击”致急性呼吸窘迫综合征（ARDS）的防治作用,为中西医结合防治呼吸道疾病提供有效依据。方法: 48只健康雄性Wistar大鼠随机分为4组:生理盐水对照组、ARDS模型组、大承气汤治疗组、地塞米松治疗组,每组12只。采用大肠杆菌脂多糖(LPS) “二次打击”建立大鼠ARDS动物模型,结合动脉血气分析、肺湿/干重(W／D)比值及肺组织病理学观察和评分,评价大承气汤的药理作用;酶联免疫吸附法（ELISA）测定血浆与支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-10水平,探讨大承气汤的药理作用和免疫调节机制。结果: (1)大承气汤可以显著提高ARDS大鼠动脉血氧分压,增加血氧饱和度,降低肺湿/干重比值和肺病理损伤,减轻肺水肿和肺部炎症反应,因而具有改善肺通气、抑制肺部炎症反应、减轻肺损伤功能。(2)大承气汤可使血浆促炎细胞因子（TNF-α、IL-1）和抗炎细胞因子（IL-10）水平同时降低,使BALF中TNF-α、IL-1水平降低同时IL-10水平却升高,因而表现出对全身炎症反应和局部炎症反应不同的免疫调节机能。结论: 大承气汤抑制肺部炎症反应除与下调全身炎症反应水平有关,同时还与促进肺部抗炎介质产生、调节肺部促炎介质/抗炎介质的平衡有关。     

Artesunate Inhibits Renal Ischemia Reperfusion-Stimulated Lung Inflammation in Rats by Activating HO-1 Pathway

Artesunate (AS), a semi-synthetic derivative of Artemisia, has been shown to exert a wide range of pharmacological effects, such as anti-inflammatory and antioxidant functions. However, the protective functions of AS on renal ischemia reperfusion injury (RIR)-stimulated lung inflammation remain unclear. In this research, acute lung injury (ALI) was stimulated by renal ischemia reperfusion injury (RIR). AS (15 mg/kg) was intraperitoneal administrated to rat 1 h before RIR stimulation. Serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, arterial blood gas and biochemistry, lung wet/dry weight ratio and MPO activity, total cell number and protein concentration in BALF, tissue histology, and NF-κB expression were determined. The results indicated that serum and pulmonary NO, MDA, IL-6, MIP-2, and PGE₂ levels, lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF enhanced after RIR stimulation. These alterations were mitigated by AS. AS attenuated lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF. AS attenuated RIR-stimulated pulmonary NF-κB phosphorylation. In addition, these previously mentioned actions of AS were antagonized by suppressing HO-1 pathway. However, RIR-stimulated arterial blood gas and biochemistry and lung histopathology were also attenuated by AS. In summary, AS inhibited RIR-stimulated lung inflammation by activating HO-1 pathway.     

Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces Soluble Tumor Necrosis Factor Receptor Production through Tumor Necrosis Factor Alpha-Converting Enzyme Activation

Primary Mycobacterium tuberculosis infection results in granuloma formation in lung tissue. A granuloma encapsulates mycobacterium-containing cells, thereby preventing dissemination and further infection. Tumor necrosis factor alpha (TNF-α) is a host-protective cytokine during M. tuberculosis infection due to its role in promoting and sustaining granuloma formation. TNF activity is regulated through the production of soluble TNF receptors (sTNFRI and sTNFRII). Therefore, we examined the potential production of endogenous sTNFRs during M. tuberculosis infection. Using the murine model of aerosol M. tuberculosis infection, we determined that levels of sTNFR production were elevated in bronchoalveolar lavage fluid 1 month following infection. An investigation of M. tuberculosis cell wall components identified that the known virulence factor mannose-capped lipoarabinomannan (ManLAM) was sufficient to induce sTNFR production, with sTNFRII being produced preferentially compared with sTNFRI. ManLAM stimulated the release of sTNFRs without TNF production, which corresponded to an increase in TNF-α-converting enzyme (TACE) activity. To determine the relevance of these findings, serum samples from M. tuberculosis-infected patients were tested and found to have an increase in the sTNFRII/sTNFRI ratio. These data identify a mechanism by which M. tuberculosis infection can promote the neutralization of TNF and furthermore suggest the potential use of the sTNFRII/sTNFRI ratio as an indicator of tuberculosis disease.     

骨髓来源间充质干细胞培养上清液减轻脂多糖诱导的小鼠急性肺损伤

 目的:观察经尾静脉输注骨髓间充质干细胞培养上清液（MSCs CdM）对脂多糖(LPS)诱导的小鼠急性肺损伤的治疗作用及其机制。方法:采用全骨髓培养法分离纯化骨髓间充质干细胞,传至第3代时观察细胞形态,流式细胞术检测细胞表面标志,并且收集上清液用超滤离心管进行离心。30只BALB/c小鼠随机分为对照组、 LPS模型组和MSCs CdM治疗组。对照组腹腔内注射生理盐水（0.01 mL/g）,LPS组和MSCs CdM治疗组腹腔内注射LPS（5 mg/kg,0.01 mL/g）制备急性肺损伤模型。造模1 h后经尾静脉输注MSCs CdM（MSCs  CdM治疗组）或生理盐水 （LPS组或对照组）300 μL。6 h后处死小鼠,留取标本检测肺组织病理形态学、肺组织湿干重比（W/D）、支气管肺泡灌洗液（BALF）中蛋白含量、血清及BALF中细胞因子水平和肺组织中髓过氧化物酶(MPO)的活性。结果:与对照组比较,LPS处理后肺组织病理损伤严重,BALF中蛋白、血清肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)含量、肺组织中MPO活性及肺组织湿干重比均显著升高。与LPS组比较,MSCs CdM治疗组肺组织病理损伤程度减轻,BALF中蛋白、血清TNF-α和IL-6含量、肺组织中MPO活性及肺组织湿干重比均显著降低,而BALF中白细胞介素10（IL-10）和角质细胞生长因子（KGF）水平显著高于LPS组和对照组。结论:骨髓间充质干细胞培养上清液可有效减轻LPS诱导的急性肺损伤,其作用机制可能与其调节肺部TNF-α、IL-6、IL-10和KGF的水平有关。     

中性粒细胞胞外诱捕网在新生大鼠急性肺损伤中的作用

目的:探讨中性粒细胞胞外诱捕网(NETs)在新生大鼠急性肺损伤(ALI)中的作用。方法:取出生7 d的SD大鼠30只,按照随机数字表法分成生理盐水对照组、ALI组及ALI+脱氧核糖核酸酶(Dnase)组,每组10只。ALI组用脂多糖(LPS)以20 mg/kg的剂量腹腔注射,ALI+Dnase组则在注射LPS后即腹腔注射Dnase(5 mg/kg)。给药6 h后,水合氯醛麻醉大鼠,收集支气管肺泡灌洗液(BALF),荧光酶标仪检测BALF中游离DNA(cf-DNA)的含量;右肺组织固定于4%多聚甲醛中,HE染色观察各组大鼠肺组织形态结构;左肺组织制备肺组织匀浆,酶联免疫吸附测定(ELISA)法检测肺组织匀浆中白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)的含量;使用免疫荧光法与Western blot检测各组大鼠肺组织中瓜氨酸化组蛋白H3(CitH3)及髓过氧化物酶(MPO)的生成情况。结果:与对照组相比,ALI组与ALI+Dnase组中cf-DNA、CitH3、MPO、IL-6及TNF-α水平均升高(P<0.05),肺组织中炎性细胞浸润严重;与ALI组相比,ALI+Dnase组新生大鼠肺组织中cf-DNA、Cith3、MPO、IL-6及TNF-α水平降低(P<0.05),ALI+Dnase组炎症浸润程度降低。结论:新生大鼠ALI中,NETs水平为反映肺组织损伤的重要指标,NETs可能为治疗新生儿ALI的新靶点。     

Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury

Acute lung injury (ALI) is a severe illness with excess mortality and no specific therapy. Protective actions were recently uncovered for docosahexaenoic acid-derived mediators, including D-series resolvins. Here, we used a murine self-limited model of hydrochloric acid-induced ALI to determine the effects of aspirin-triggered resolvin D1 (AT-RvD1; 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) on mucosal injury. RvD1 and its receptor ALX/FPR2 were identified in murine lung after ALI. AT-RvD1 (∼0.5–5 μg kg⁻¹) decreased peak inflammation, including bronchoalveolar lavage fluid (BALF) neutrophils by ∼75%. Animals treated with AT-RvD1 had improved epithelial and endothelial barrier integrity and decreased airway resistance concomitant with increased BALF epinephrine levels. AT-RvD1 inhibited neutrophil–platelet heterotypic interactions by downregulating both P-selectin and its ligand CD24. AT-RvD1 also significantly decreased levels of BALF pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, Kupffer cells, and tumor necrosis factor-α, and decreased nuclear factor-κB-phosphorylated p65 nuclear translocation. Taken together, these findings indicate that AT-RvD1 displays potent mucosal protection and promotes catabasis after ALI.     

Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice

Objective

Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods

Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were detected by western blot.

Results

Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS.

Conclusion

The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment.     

Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.     

油酸型急性呼吸窘迫综合征大鼠血清及肺组织IL-4、IL-10、IL-12水平的变化

目的:观察IL-4、IL-10、IL-12在大鼠油酸型急性呼吸窘迫综合征(ARDS)不同时间血清及肺组织中的变化规律。方法:经舌下静脉注射油酸复制大鼠ARDS模型,用酶联免疫吸附试验测定不同时间血清及肺组织匀浆上清液中IL-4、IL-10和IL-12水平。结果:注射油酸4h、8h、16h组血清及肺组织中IL-10、IL-12水平均明显高于对照组(P＜0.01或0.05);但注后16h组血清和注后8h组肺组织中IL-10水平均明显低于4h组(P＜0.05);血清中IL-4水平在注射油酸4h、8h组均明显高于对照组(P＜0.01或0.05);而16h组则明显低于4h组(P＜0.05);肺组织中IL-4水平在4h、8h、16h组均明显高于对照组(P＜0.01),而16h组则明显低于8h组(P＜0.05)。肺系数和肺组织病理学变化在注射油酸后4h组改变最明显。结论:IL-4、IL-10和IL-12在大鼠油酸型ARDS炎症过程中可能起重要作用;ARDS时促炎性和抗炎性细胞因子相继产生,而两者相互作用的失衡与ARDS肺损伤的关系值得深入探索。     

山莨菪碱预处置对大鼠ARDS血清及肺组织中细胞因子的影响

目的 观察山莨菪碱(654-2)预处置对大鼠油酸型急性呼吸窘迫综合征(ARDS)血清及肺组织中IL-6、IL-8、TNF-α及IL-10的影响,探讨654-2治疗ARDS的理论基础。方法 经舌下静脉注射油酸复制大鼠ARDS模型,用酶联免疫吸附试验测定血清及肺组织匀浆上清液中IL-6、IL-8、TNF-α和IL-10水平。结果 ARDS组大鼠血清IL-6、TNF-α、IL-10含量和肺组织匀浆上清液中IL-6、IL-10含量明显高于对照组(P<0.01或0.05)。654-2预处置组血清和肺组织中IL-10水平显著高于对照组(P<0.01或0.05)。654-2预处置组血清和肺组织中IL-6、TNF-α含量明显低于ARDS组(P<0.01或0.05),而IL-8和IL-10含量两者无显著性差异。结论 IL-6、IL-8、TNF-α及IL-10在大鼠油酸型ARDS炎症过程中可能起重要作用,654-2可能通过抑制IL-6、TNF-α过度分泌而减轻肺损伤。     

老年心力衰竭患者血清炎症因子的变化

目的： 研究老年心力衰竭患者血清肿瘤坏死因子α（TNF-α）、可溶性肿瘤坏死因子受体I（sTNFRI）、白细胞介素6（IL-6）、白细胞介素10（IL-10）、转化生长因子β_I（TGF-β₁）水平与心功能状态之间的关系。 方法： 采用双抗夹心ELISA法测定112例老年心力衰竭患者及60例健康老年人的血清TNF-α、IL-6、sTNFRI、IL-10和TGF-β₁水平，同时采用心脏超声仪测定左心室舒张末期内径（LVEDD）和左心室射血分数（LVEF）。 结果： (1)老年心力衰竭患者的血清TNF-α、IL-6、sTNFRI、IL-10和TGF-β1水平明显高于对照组（P＜0.05,P＜0.01），且随着心功能的恶化逐渐升高（P＜0.05,P＜0.01）。(2)心力衰竭患者血清TNF-α/sTNFRI、IL-6/IL-10的比值显著高于对照组（P＜0.05, P＜0.01），而且随着心功能的恶化逐渐升高（P＜0.05,P＜0.01）。(3)血清TNF-α和IL-6水平与LVEDD呈显著正相关（P＜0.05），与LVEF呈负相关（P＜0.05）。 结论：在老年心力衰竭患者中，血清促炎症性细胞因子与心功能状态密切相关，促炎症细胞因子与抗炎症细胞因子的平衡向炎症方面偏移，两者的改变能够反映心功能的变化。