Objective To investigate the inhibitory effects of aerosol budesonide on the expression of indoleamine 2,3 dioxygenase (IDO),airway inflammation,and airway hyperresponsiveness in a murine model of bronchial asthma (asthma).Methods 18 BALB/c mice were randomly divided into 3 groups,including the control group,ovalbumin (OVA) group and budesonide group.Mice were sensitized and challenged by OVA.24 h after the last challenge,airway responsiveness to acetylcholine chloride (Ach) was measured.Hematoxylin & eosin staining was used to assess the inflammatory cell infiltrates.Levels of Th2 cytokines (IL-4 and IL-13) in bronchoalveolar lavage fluid (BALF),and total IgE and OVA-specific IgE (OVA-sIgE) in serum were relevantly detected by ELISA.The protein expression of IDO was determined by western blot analysis.Results The airway resistance in the OVA group was obviously increased in a dose-dependent manner following administration of Ach,whereas only a slight increase could be detected in the control group.Treatment with budesonide led to a sharp decrease in airway resistance compared with the OVA group (P ＜0.05).Total IgE and OVA-sIgE in serum,total inflammatory cells and differential eosinophils as well as Th2 cytokines in BALF were significantly increased in the OVA group.These inflammatory indices were remarkably decreased by treatment with budesonide (P ＜0.05).The pulmonary expression of IDO was apparently declined in the OVA group.Treatment with budesonide enhanced the pulmonary expression of IDO in comparison with the OVA group (P ＜ 0.05).Conclusions Budesonide could inhibit the airway inflammation and hyperresponsiveness by upregulating the expression of IDO in allergic asthma.
Objective To investigate the effect of taurine on bronchial asthma (asthma) rats airway reactivity.Methods Forty SD rats were randomly divided into four groups:control group,asthma group,taurine intervention group and dexamethasone treatment group,ten rats in each group.The rats were sensitized and challenged with ovalbumin (OVA) to establish chronic asthma model.Thirty min before each airway challenge,taurine intervention group and dexamethasone treatment group rats were respectively administered intraperitoneally with TAU 500 mg/kg and DXM 5 mg/kg daily for 5 consecutive weeks.The mice were sacrificed 24 h after last aerosol challenge.The sections were stained with HE to assess the morphology change and airway inflammation.ELISA was used to measure IL-13 levels in serum.The Power Lab tension transducer was used to test the response on isolated trachea strips at the different concentrations of acetylcholine and ipratropium bromide.Immunohistochemistry was used to detect the expression of the 12/15-LO in the left lung.Results Airway epithelium was incomplete,part of the mucosa epithelial cell fell off,the mucosa was edema,and mass inflammatory cells infiltration in asthmatic group.Taurine intervention,similar with dexamethasone treatment,can ameliorate the above mentioned symptoms significantly.Compared with asthma group,the response of isolated trachea strips and the levels of IL-13 (P ＜0.05) in serum and 12/15-LO (P ＜0.05) in left lung significantly decrease in taurine intervented rats.Compared with dexamethasone treatment group,taurine intervention group have similar effect (P ＞0.05).Conclusions Taurine could alleviate OVA-induced asthma,which might through decreasing airway tension,restraining mediators of inflammation,and inhibiting arachidonic acid metabolism in lung tissue.
Bronchial asthma (asthma) is a chronic and complex airway inflammatory disease characterized by airway hyper-responsiveness.Current asthma therapies are limited to specific disease manifestations,highlighting the importance of developing treatments with broader treatment applications.CD4-T lymphocytes,which produce a characteristic repertoire of cytokines,play a critical role in the development of airway inflammation,mucus production and airway hyper-responsiveness in asthma.Recently,it has been demonstrated that heat shock protein 60 (HSP60) could mediate CD4-T lymphocyte differentiation,suggesting that HSP60 can be targeted in the development of novel anti asthma medications,especially for the treatment of severe disease or refractory patients.This review summarizes the current knowledge regarding the relationship between HSP60 and asthma.
Objective To investigate the therapeutic effect of low-dose inhaled corticosteroids plus low-dose theophylline to the smokers with moderate bronchial asthma (asthma).Methods To screen 80 asthma cases in the clinic,and they were randomized to two groups:the observed group and the control group.The observed group consisted of smokers and the observed group consisted of non smokers.They all accepted inhalation budesonide 200 μg/d plus aminophylline tablet (0.1 gtid po) for 3 months.The ACT,PEF,FEV1 ％ predicted,IL-4,IL-5 and IgE of peripheral blood were compared before and after treatment.Results Before and 3 months after the treatment,the ACT,PEF,FEV1％ predicted,IL-4,IL-5,IgE value for the observed group were (14.3±2.4) and (21.7±2.0),(255.9±99.7) L/min and (290.3±105.2) L/min,(66.5±4.7) and (72.9±5.4),(14.5±3.2) ng/L and (12.3±3.4) ng/L,(27.2± 6.4) ng/L and (24.2±5.8) ng/L,(82.7 ± 16.8) IU/ml and (67.1 ± 14.3) IU/ml,respectively,and those for the control group were (13.8 ± 2.2) and (21.5 ± 1.4),(279.1 ± 103.3) L/min and (321.3±110.4) L/min,(68.8±5.8) and (74.8±5.5),(13.4±2.9) ng/L and (11.4±2.8)ng/L,(26.5±6.9) ng/L and (22.8± 6.2) ng/L,(78.8±18.2) IU/ml and (66.4±17.8) IU/ml,respectively,which were remarkably improved in both groups (P ＜ 0.05).There were no differences between two groups (P ＞0.05).Conclusions Compared with non-smokers,the smokers with moderate bronchial asthma treated with ICS plus low dose theophylline showed similar therapeutic effects in the improvement of clinical symptoms,increasing of lung function and control of the airway inflammation.
Objective This study measured the vitamin D levels in patients with allergic asthma and compared the results with the general population.To determine the relationship between serum concentrations of vitamin D and pulmonary function,TIgE,and airway responsivenss,the relationship between TIgE and airway responsivenss.Methods Vitamin D and TIgE levels were assessed in 41 patients with allergic asthma.There was no control group,and the study results were compared with the standard value.At the same time,lung function,airway hyperresponsiveness (AHR) were performed.Comparison the correlation of vitamin D and TIgE,pulmonary function and airway responsivenss,the relationship between TIgE and airway responsivenss.Results The prevalence of severe vitamin D3 (23.10± 23.15) deficiency was significantly in patients with allergic asthma than the standard value,vitamin D3level were positive correlated with FEV1 (r =0.428,P ＜0.01).There was no correlation on vitamin D level and TIgE (r =-0.265,P ＞0.01) and negtive correlated with AHR(r =-0.559,P ＜0.01).Here was negtive correlated with TIgE and AHR (r =0.578,P ＜ 0.01).Conclusions Vitamin D deficiency was highly prevalent in asthma patients,and vitamin D status was associated with lung function,AHR.Unlike the childen,there was no correlation on vitamin D level and TIgE in adult.
Previous studies of association of beta 2 adrenergic receptor gene (β2-AR) with bronchial asthma was focused in the coding region polymorphisms,these polymorphisms may be associated with the asthmatic susceptivity,phenotype and response to treatment.But there are many inconsistent results,and these differences could not be fully explained by β2-AR gene coding region and the 5'untranslated region polymorphism.In recent years a large number of studies have found not only the coding region,5'and 3' untranslated region polymorphisms can also change the β2-AR function and affect treatment response in asthma.All variants that complete haplotypes on the β2-AR gene should be identified and analyzed.This article reviews the recent development of β2 AR gene coding region,5'and 3' untranslated region polymorphisms,especially the 3'untranslated region of poly-C repeat length variation on patients with asthma plays an important role on pulmonary function and β2-AR agonist treatment response.
Bronchial asthma(asthma)is a common disease of respiratory system.Due to its high incidence and a considerable financial burden,people's health have seriously affected.So far,etiology and pathogenesis of asthma is not clear,therapeutic method and clinical efficacy are poor in patients with difficult-to-treat asthma.This article reviews the highlights of definition,phenotype and treatment of difficult-to-treat asthma in recent years.
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell-surface receptor expressed on neutrophils and monocytes,that belongs to the member of immunoglobulin superfamily,that connected its unknown ligand could amplify the inflammation responses.Recently it is found that the soluble TREM-1 (sTREM-1) as biomarker and respiratory disease are closely connected.This review mainly summarizes the TREM-1 of structure,biological expression and the relationship with respiratory disease.
Objective To investigate the effects of TGF-β1 type Ⅰ receptor antagonist on airway inflammation and remodeling in murine model of chronic bronchial asthma (asthma),providing a potential approach for the therapy of asthma.Methods Forty BALB/c mice were randomly divided into 4 groups:a normal group,an asthma group,a budesonide group and a SB 431542 group,with 10 mice in each.The mice were sensitized and challenged with ovalbumin (OVA) to establish murine model of chronic asthma.The budesonide group and SB 431542 group were intervened with aerosolized budesonide and intranasal SB 431542 three times a week respectively.Alterations of the airway inflammation and collagen deposition were observed by the means of haematoxylin eosin (HE) and Masson staining.The global cells were quantified by periodic acid schiff (PAS).The expression of α-smooth muscle actin (α-SMA) in lungs was evaluated by immunohistochemistry.The levels of interleukin (IL)-4,IL-5,TGF-β1,MMP-9 and TIMP-1 in BALF,and the total level of IgE in serum were evaluated by enzyme linked immunosorbent assay (ELISA).The protein expression of Smad3,phosphorylation of Smad3 (p-Smad3)and Smad7 were detected by Western blot.Results There were mass inflammatory cells infiltration,airway stenosis,bronchial smooth muscle hypertrophy and collagen fiber increasing in the asthmatic group,these alterations were lessen in budesonide group.The inflammatory cells infiltration in SB 431542 group were more relievable than asthma group,but still worse than budesonide group,while the bronchial smooth muscle hypertrophy and collagen fiber increasing were equal to budesonide group (P ＞0.05).A significant increase in the number of PAS-positive epithelial cells was found in the asthma group compared with the control group (P ＜0.05).Treatment with budesonide or SB 431541 reduced the number of PAS positive cells (P ＜0.05).The area of the α-SMA-stained smooth muscle layer in the asthmatic group were significantly larger than those in the control group (P ＜ 0.05),while administration of budesonide or SB 431542 reduced the α-SMA immunostained area (P ＜0.05).The levels of total serum IgE and BALF IL 4,IL-5,TGF-β1 were increased in asthma group compared to control group(P ＜0.05),but there were no significant differences between the asthma group and SB 431542 group (P ＞0.05),while the levels of mentioned indexes above were decreased in budesonide group (P ＜0.05).MMP 9 and TIMP-1 levels were significantly raised in asthma group (P ＜0.05),both budesonide and SB 431542 intervene could reduced MMP-9 and TIMP-1 levels (P ＜0.05).The lung Smad3 protein were expressed similarly in all groups (P ＞0.05),but the p-Smad3 in budesonide group were higher then control group (P ＜0.05),while it was significantly decreased in the budesonide group and the SB 431542 group(P ＜0.05).The Smad7 protein was observed lower in asthma group compared to the control group(P ＜0.05),administration of budsonide or SB 431542 could restore the express of Smad7 protein (P ＜0.05),there were no significant differences between the budsonide group and SB 431542 group (P ＜0.05).Conclusions SB 431542 alleviated the extracellular matrix deposition and airway smooth muscle thickening,partially by regulating the levels of MMP 9 and TIMP 1.However,we did not observe significant improvement of inflammation infiltration in asthmatic mice airway,this may imply that airway inflammation in asthma is not dependent on TGF-β1/Smads signaling pathway.
Objective To explore the clinical value of bronchoalveolar lavage fluid (BALF) pathogen culture and drug susceptibility testing in the treatment of bronchiectasis accompany with bronchial asthma.Methods Select 90 cases inpatients with bronchiectasis and bronchial asthma.Collect their BALF for pathogens culturing and antibiotic susceptibility testing.Results 55 of the 90 cases patients is positive in pathogen detection(61.1％),and 57 strains in all.54 strains Gram negative bacilli (94.7 ％),mainly in P.aeruginosa,followed by Acinetobacter baumannii,2 strains fungi (3.5 ％),both Aspergillus,1 strains Gram positive cocci (1.8％),Staphylococcus aureus.Two cases are mixed infection,Acinetobacter baumannii merging Staphylococcus aureus and Amur Pseudomonas merging Pseudomonas aeruginosa.Results of the Susceptibility test:53 strains Gram-negative bacilli are most sensitive to tobramycin,cefoperazone sulbactam,imipenem,and are most resistant to cefotaxime,cotrimoxazole,L levofloxacin,maltophilia oligotrophic food Aeromonas is 100％ sensitive to Llevofloxacin,minocycline and cotrimoxazole,Aspergillus is 100％ sensitive to amphotericin B,itraconazole,voriconazole,there is only 1 strains Gram-positive cocci,not deeply studied due to weak results of drug susceptibility.Conclusions The main pathogens cultured of BALF in patients with bronchiectasis accompany with bronchial are Gram-negative bacilli,fungal infection also reveals,and Gram positive cocci is less,although two kinds or more than two kinds of mixed bacterial irnfection is few,mixed culture infection is an indication of pathogens that a variety of antimicrobial agents may be increased,the results of drug sensitive for clinical treatment of bronchiectasis combined bronchial asthma have important guiding significance; there will be a larger clinical application value because of targeted sampling site,providing reliable results,and high cultivating positive rate.At the same time,bronchoalveolar lavage can help clear infectious secretion,improving bronchial obstruction and reducing local pathogen quantity and concentration,and also help improve their breathing symptoms and control the infection.
Objective To investigate whether simvastatin may influence human airway smooth muscle cell proliferation induced by platelet activating factor through ROS formation.Methods Cell proliferation was analyzed according to the protocol of CCK-8assay.Fluorescence microscope was used to observe fluorescence intensity of each group.Intracellular reactive oxygen species was measured by the flow cytometer using an oxidationsensitive fluorescent probe , 2′7′-dichlorofluorescin diacetate ( DCFH-DA ) .Results Our data demonstrated that PAF induced HASMCs proliferation with the maximal effect seen at 10-6 M and 24h , the proliferation rate was ( 1.77±0.51 ) as fold as the control group.Simvastatin ( at the concentration of 10-5 M ) was ( 0.67±0.18 ), inhibited HASMCs proliferation induced by PAF ( P 0.01 ) .Compared with the negative control group ( 76.79±6.05 ), PAF-treated group ( 98.89±1.28 ) led to a significant increase in DCF fluorescence , PAF combined with simvastatin group ( 66.40±2.87 ) decreased ROS level ( P 0.01 ) .Conclusions Simvastatin inhibited HASMCs proliferation induced by PAF partly through ROS formation.
Objective To seek the cytological classification and airway pathogenic bacteria colonization,infection situation of bronchoalveolar lavage fluid (BALF) in patients with refractoryasthma.Methods Select 138 inpatients with refractory asthma which measure upto national standard,to test the BALF cells classification and bacterial culture through the bronchoscope alveolar lavage.Results ① The inflammatory cells classification of BALF:Neutrophile granulocyte 63.78 ± 30.02,Eosinophilic granulocyte 2.70 ± 4.04,Lymphocyte 5.93 ± 6.48,Alveolarmacrophages 27.21 ± 31.87,display neutrophils increased obviously.② Influence of pathogens on airway inflammation:the mean value of Neutrophils in patients with positive pathogens are an increase compared with patients with negative,but no statistically significant differences,Eosinophils mean value are low compared wiht patients with negative,the differences was statically significant (P ＜ 0.01).③ The inflammatory cells classification of BALF:Classification standard by airway inflammation,138 cases of 24 cases of all the 138 cases are Eosinophil asthma,account for 17.38％,46 cases with Neutrophilic asthma,account for 33.33％,26 cases of Myeloid less asthma,18.84％,42 case with Mixed grain cell asthma,30.43％.General status in the group,Neutrophils group and few cell group have a longer course of disease,older ages,lower cortisol,smoking rateis higher in Neutrophils group.④Previous treatment condition of each inflammation type:patients in Neutrophils groupwith used much more systemic hormones are higher than the Eosinophils group,while the volume of inhaled steroids used less than eosinophils group.⑤Etiology test results:23 cases of pathogenic bacteria were checked out in 138 patients,account for 16.7％,Gram negative bacilli isolated from most of them,a total of 16 cases,percent of total pathogen detection 69.6％.Conclusions ① There is a special table types of airway inflammation cells in patients with refractory asthma,dominated by Neutrophils ncreased type,the reason for this may be related to bacterial infection and colonization,hormone use,smoking,age,course of disease.②Respiratory tract bacterial infection and colonization has a certain role in the pathogenesis of refractory asthma.
Nod-like receptors (NLRs) are intracellular sensors that respond to a variety of pathogen and intracellular danger signals to induce innate immune responses.NLRC5,a number of NLRs family,has recently been identified to be an important regulator of nuclear factor-κB,type Ⅰ interferon,inflammation signaling pathways,and the expression of MHC class Ⅰ genes.It plays a pivotal role in the innate immune responses and adaptive immune responses.This paper summarizes the latest researches about NLRC5.
Sphingolipids are molecules ubiquitously expressed in all kinds of eukaryotic cell membranes.Initially they were characterized as structural components of cell membranes.While with the development of research,sphingolipids have emerged as sources of vital singaling molecules.Sphingosinel-phosphate (S1P) is one of sphingolipid metabolites,which has roles as potent bioactive messengers involved in cell differentiation,proliferation,apoptosis and angigenesis.S1P plays a crucial role in the mechanism of bronchial asthma.A newly recognized addition to the repertoire of FcεRI-mediated signaling events is the activation of sphingosine kinase leading to the generation of S1P from sphingosine.It is also demonstrated that S1P provokes the contraction of airway smooth muscle cells and airway remodeling.These novel pathways represent exciting potential therapeutic targets in the treatment of bronchial asthma and are described in the present review.
Asthma is a bronchoconstriction reversibility,lung inflammation and airway remodeling for characteristics of chronic airway inflammatory disease.Excessive mucus secretion lead to obstruction of the airway,lung function decline,airway remodeling and increase infection.Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS)produce cause airway inflammation,airway responsieness,airway microvascular high permeability and high airway mucus secretion,and tissue damage and the change of the form.Reduce oxidative stress or increase antioxidant that can reduce airway eosinophils,reduce mucus secretion,reduce bronchial high reaction.Oxidative stress and asthma airway mucus secretion relationship high application were introduced in this paper.
Objective To explore the effect of mental intervention on the survivors in earthquakes with post-traumatic stress disorder(PTSD)and acute bronchial asthma.Methods 40 patients with PTSD and acute bronchial asthma were divided into 2 groups,control group and experiment group.The control group was treated with conventional therapy of bronchial asthma,and the experiment group was treated with mental intervention and conventional therapy of bronchial asthma,respectively.PCL-C、ACQ5、FEV1 ％pred、PEF％ pred.EOS in Peripheral blood of two groups were compared.Results PCL-C、ACQ5 、FEV1 ％ pred and PEF％ pred of the experiment group were improvement,obviously,compared with that of the control group,respectively.The difference in two group was statistical significance (P ＜0.05),but the difference of EOS in Peripheral blood in two group was no noticeable difference (P ＞ 0.05).The value of PCL-C from the experiment group showed a positive correlation with the value of ACQ5 (r =0.61,P ＜0.05),and a negative correlation with the level of FEV1 ％ pred and PEF％ pred,respectively.(r =0.53,r =-0.57,respectively.all P ＜0.05),and no correlation with the level of EOS (P ＞0.05).Conclusions The effect of mental intervention united conventional therapy of bronchial asthma was better than the conventional therapy,but had no obvious improvement for EOS in Peripheral blood.
目的 探讨刺槐素(Acacetin)对肿瘤坏死因子-α(TNF-α)诱导的人气道平滑肌细胞(HASMCs)分泌、表达单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)的影响及可能的机制.方法 CCK-8法测HASMCs增殖活性;酶联免疫吸附法(ELISA)测HASMCs上清液中MCP-1含量;实时荧光定量PCR(RT-PCR)检测MCP-1 mRNA表达量;蛋白印迹法(Western blot)检测HASMCs中磷酸化P65(P-P65)蛋白的表达情况.结果 ①Acacetin及NF-κB抑制剂JSH-23均能显著降低TNF-α诱导的HASMCs MCP-1生成,且Acacetin的抑制作用具有浓度依赖性(P＜0.05);②同时,Acacetin及JSH-23均能显著减少TNF-α诱导的MCP-1mRNA的表达(P＜0.05);③Acacetin 能显著降低TNF-α引起的HASMCs P65蛋白磷酸化(P＜0.05).结论 降低NF-κB通路的活化水平可能是Acacetin抑制TNF-α诱导HASMCs合成、分泌MCP-1及其mRNA,从而发挥抗炎作用的机制之一.
目的 观察应用布地奈德/福莫特罗粉吸入剂对COPD患者的白介素-17(interleukin 17,IL-17) 、肿瘤坏死因子受体75(tumor necrosis factor receptor 75,TNF-R75)、基质金属蛋白酶(matrixmetalloproteinase-9,MMP-9)和肺功能及生活质量的影响.方法 2011年6月至2012年6月入住我科,符合中华医学会呼吸病学分会COPD诊断标准且肺功能分级为中重度的患者40例,在导入治疗第7天后用布地奈德/福莫特罗粉吸入剂160/4.5 μg,每次2吸,每日2次.于用药前及用药第7、60、90天采用圣乔治评分、6分钟步行试验,酶联免疫吸附法测定外周血细胞因子:TNF-R75、IL-17、MMP-9.结果 COPD患者使用布地奈德/福莫特罗粉吸入剂第60天时,FEV1%pred明显升高,圣乔治呼吸问卷评分、6分钟步行试验距离明显改善,与治疗前比较差异有统计学意义(P＜0.05).治疗第90天时FEV1%pred继续改善(与治疗前比P＜0.01),FEV1/FVC仅在治疗第90天时与治疗前比较有明显改善.COPD患者使用布地奈德/福莫特罗粉吸入剂后第7、60、90天患者MMP-9与治疗前相比差异无统计学意义(P＞0.05).治疗后第90天TNF-R75、IL-17与治疗前比较差异有统计学意义(P值均＜0.05).结论 COPD患者长期规律使用布地奈德联合福莫特罗治疗可以改善患者生活质量评分及肺功能.
Objective To observe the influence of Hua Tan and Ping Chuan Decoction (HTPCD) on the expression of SCF in the lungs of allergic-induced asthmatic mice.Methods Fifty healthy female BALB/c mice were randomly divided into five groups:the normal control group,the model group,the prednisone acetate group,the HTPCD group,the HTPCD and prednisone acetate group (n-10).Asthmatic mice were sensitized by injecting with nebulized ovalbumin (OVA).We estimated the pathological change in lungs of each group.The protein expressions of SCF were detected by immunohistochemical staining.Results The levels of SCF in allergic-induced asthmatic mice by treated were significantly decreased compared with the model group,and there were statistical differences between the therapeutic group and the model group(P ＜0.01).While the results in the mixture group without obvious changing than those in the prednisone acetate group (P ＞ 0.05).Conclusions HTPCD can decrease the level of SCF,so HTPCD has the role of antagonizing airway inflammatory of asthma.HTPCD can effectively improve the treatment of the prednisone acetate so as to greatly decrease the dose of the prednisone acetate.
Cyclic adenosine monophosphate (cAMP) is the firstly discoveried second messenger.cAMP controls a range of diverse physiological processes,including metabolicevents,calcium handling,learning and memory,cellgrowth and differentiation,apoptosis,and inflammation.Protein kinase A (PKA) had been considered as the sole downstream target of cAMP.However,recent studies have demonstrated thatEpac,a novel cAMPmediator,regulates manyphysiological processes either alone and (or) in concert with PKA.In this review,we will discuss the roles and probable mechanisms of Epac in the management of asthma in order to provide beneficial clue to find new therapy targets.
