细胞因子抗体在哮喘治疗中的进展

哮喘是由多种细胞及其细胞因子参与的气道慢性、复杂的炎症性疾病,以气道炎症,黏液分泌增加,气道高反应性为特点,并且导致反复发作性的喘息、胸闷、咳嗽和气促等症状的发生。自从1980年以来全球哮喘的发病率普遍上升,特别是在儿童中更是明显上升。它已逐渐成为绝大多数工业化国家的主要疾病,影响着成千上万患者的生活质量。目前哮喘的药物治疗中普遍包括肾上腺糖皮质激素,这类药物非特异性地抑制了免疫系统,不仅大大地增加了感染的几率,长期使用这类药物还可能会导致骨质疏松、高血压等疾病,所以最近有很多研究从哮喘发病的分子机制着手,利用各种细胞因子抗体为哮喘的治疗提供了许多更有效、更特异的治疗手段。     

小鼠哮喘模型中补体C5a对IL-17表达的调节作用

目的 探讨小鼠哮喘模型中补体C5a对IL-17表达的调节作用.方法 用卵清蛋白(OVA)致敏、激发的方法 建立Balb/C小鼠哮喘模型.用体内抗体中和试验,观察致敏前中和炎症介质补体C5a的功能是否影响小鼠肺泡灌洗液中IL-17细胞因子的表达水平,并探讨其机制.结果 病理结果 显示模型组小鼠的肺组织出现肺泡腔扩张、腔内大量炎性细胞的浸润.小鼠致敏前给予抗C5a抗体干预上调了肺部IL-17及IL-6 的表达,导致肺炎症明显加重.结论 小鼠哮喘模型中体内C5a分子对IL-17表达具有负调节作用.     

模拟临床的中性粒细胞性激素抵抗型支气管哮喘小鼠模型的建立及意义

目的建立一种模拟临床的中性粒细胞性激素抵抗型支气管哮喘(哮喘)小鼠模型并探讨其意义。方法采用屋尘螨(house dust mite,HDM)和脂多糖(lipopolysaccharide,LPS)混合液,气管内给药建立哮喘小鼠模型。将18只雌性C57BL/6小鼠按照数字表法随机分为对照组、哮喘组(HDM+LPS)和地塞米松(dexamethasone,Dex)组(HDM+LPS+Dex)。肺功能仪测定小鼠气道阻力,HE染色观察肺组织炎症细胞浸润,过碘酸-雪夫染色(PAS)观察杯状细胞增生,瑞氏染色检测BALF炎症细胞总数及分类计数,聚合酶链式反应(PCR)和酶联免疫吸附试验(ELISA)检测肺组织和BALF炎症因子。流式细胞术检测肺组织Th17细胞分化。结果HE染色显示,哮喘组肺组织炎症较对照组显著增高(P<0.05),地塞米松组肺组织炎症较哮喘组稍减轻(P>0.05);BALF细胞分类计数显示,哮喘组炎症细胞(除外嗜酸粒细胞)浸润较对照组显著增加[炎症细胞总数分别为(2797±400)×106/L和(105±75)×106/L,中性粒细胞计数分别为(1151±395)×106/L和(12±6)×106/L,淋巴细胞计数分别为(897±135)×106/L和(11±5)×106/L,巨噬细胞计数分别为(215±51)×106/L和(34±16)×106/L,均P<0.05],地塞米松组肺组织炎症细胞总数及巨噬细胞计数较哮喘组显著下降[炎症细胞总数(1140±418)×106/L vs(2797±400)×106/L,巨噬细胞计数(117±31)×106/L vs(215±51)×106/L,均P<0.05],但淋巴细胞和中性粒细胞计数无统计学意义[淋巴细胞计数(587±208)×106/L vs(897±135)×106/L,中性粒细胞计数(294±134)×106/L vs(1151±395)×106/L,均P>0.05];免疫组织化学检测结果同样证实,地塞米松组肺组织中性粒细胞浸润较哮喘组不能被有效抑制;哮喘组和地塞米松组气道阻力较对照组均显著增高(P<0.05),但两组间气道阻力差异无统计学意义(P>0.05);与哮喘组相比,地塞米松组肺组织Th2炎症指标显著降低(均P<0.05),而Th17细胞炎症指标有升高趋势,Th1炎症指标无显著改善;流式细胞术显示,地塞米松组肺组织Th17细胞浸润较哮喘组显著增多[分别为(5.8±1.9)%和(2.3±0.8)%,P<0.01]。结论成功建立了一种模拟临床的中性粒细胞性哮喘小鼠模型。地塞米松非但不能抑制小鼠中性粒细胞气道炎症和气道高反应性,而且促进Th17细胞分化,印证该哮喘模型存在激素抵抗。     

持续吸入变应原引起支气管哮喘小鼠免疫耐受

目的探讨吸入变应原引起支气管哮喘(简称哮喘)过敏性气道炎症免疫耐受形成的机制。方法BALB/c小鼠60只,按随机数字表法分为实验组(50只)和空白对照组(10只),实验组小鼠先给予腹腔注射卵清白蛋白(OVA)1mg,每周1次,共3周。雾化吸入OVA每天1h(含OVA80μg),连续10d。依据吸入OVA时间分为A、B、C、D、E5组,每组10只。A组雾化吸入10d后处死。B、D组继续每天1次,每次1h,每周5次,分别吸入OVA4周及8周,然后每天1h,连续10d吸入OVA后处死。C组停止吸入OVA4周后再次吸入OVA,每天1h,连续10d后处死。E组每天1次,每次1h,每周5次,吸入OVA4周,停止雾化吸入OVA4周,然后每天1h,连续10d吸入OVA后处死。测定各组小鼠支气管肺泡灌洗液(BALF)中细胞总数,嗜酸粒细胞、淋巴细胞、CD4+、CD8+、CD4+IL-10+分类及BALF中白细胞介素4(IL-4)、γ干扰素(IFN-γ)、IL-10的含量。测定血清中IL-4、IFN-γ、IL-10、OVA、IgE、IgG1、IgG2a水平,并对各组小鼠肺组织病理学进行分析。结果空白对照组BALF中嗜酸粒细胞、B淋巴细胞、CD4+IL-10+细胞分别为0.010±0.000、2.1±1.9、4.9±1.5,A组分别为0.480±0.110、5.1±2.6、5.1±2.3,B组分别为0.120±0.020、8.9±3.6、10.4±3.6,C组分别为0.560±0.050、4.7±1.7、6.3±3.1,D组分别为0.070±0.030、10.1±2.9、12.7±4.5,E组分别为0.680±0.030、5.6±3.2、6.1±3.4,各组间比较差异有统计学意义(F值分别为36.46、31.89、167.89,P均<0.01)。B、D组BALF中CD4+IL-10+细胞数与A组比较差异有统计学意义(q=5.8、6.4,P均<0.05);空白对照组BALF中IL-4、IL-10水平分别为(21±3)pg/ml、(44±12)pg/ml,A组分别为(128±23)pg/ml、(68±18)pg/ml,B组分别为(54±12)pg/ml、(127±27)pg/ml,C组分别为(133±21)pg/ml、(78±17)pg/ml,D组分别为(8±18)pg/ml、(135±34)pg/ml,E组分别为(143±26)pg/ml、(76±15)pg/ml,组间比较差异有统计学意义(F分别为37.20、143.78,P均<0.01)。B、D两组BALF中IL-10水平与A组比较差异有统计学意义(q分别为7.8、9.6,P均<0.05)。结论持续吸入变应原可使小鼠气道炎症减轻,产生免疫耐受,调节T淋巴细胞产生的IL-10参与了耐受形成。     

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8(+) T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8(+) T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8(+) T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.     

Anti-inflammatory effects of curcumin in a murine model of chronic asthma

BackgroundCurcumin, a dietary pigment responsible for the yellow colour of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects.MethodsForty-two BALB/c mice were divided into six groups: I, II, III, IV, V, and control group. All groups except the controls were sensitised and challenged with ovalbumin. Group I received nebulised saline in challenge period. Mice in groups II, III, IV, and V were administered curcumin at a dose of 10 mg/kg, curcumin 20 mg/kg, dexamethasone 1 mg/kg, and dimethyl sulfoxide 1 mg/kg, respectively, intraperitoneally once a day for the final 5 days of the challenge period. Animals were sacrificed 24 h after the last drug administration and the airway samples were evaluated histologically by light microscopy.ResultsAll histological parameters in Group III improved similar to Group IV when compared to Group I. In Group II, only thickness of epithelium was significantly lower compared with regard to Group I. All variables except epithelium thicknesses were found to be significantly better in Group III compared to Group II.ConclusionsIn our study, we demonstrated that curcumin administration alleviates the pathological changes of chronic asthma. Curcumin might be a promising therapy for asthma in the future.     

不同剂量虫草活力素对大鼠支气管哮喘模型慢性气道炎症的作用机制研究

目的 对不同剂量虫草活力素(简称虫草)在大鼠支气管哮喘(简称哮喘)模型慢性气道炎症中的抑制作用及相关机制进行初步探讨.方法 Wister大鼠,随机分为对照组、单纯模型组、虫草20 mg/kg、50 mg/kg组、布地奈德(BUD)组及BUD联合虫草素干预组.卵蛋白致敏建立大鼠哮喘模型后给予药物干预8周,对各组支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)进行细胞分类计数及观察肺组织的病理变化,同时应用双抗体夹心ABC-ELISA法测定血清和BALF的哮喘相关细胞因子水平.结果 与单纯模型组比较,虫草两种剂量治疗组均降低慢性哮喘大鼠BALF的细胞总数和嗜酸粒细胞数,差异有统计学意义(P<0.05),并呈剂量相关性;HE染色显示大剂量虫草、BUD治疗组及联合用药组较单纯模型组炎症细胞浸润、平滑肌肥厚及黏膜肺组织水肿等炎症表现明显减轻;较单纯模型组,虫草治疗组血清及BALF的白介素4(IL-4)、IL-14水平下降,干扰素γ升高,差异有统计学意义(P<0.05),并呈剂量相关性.结果 一定剂量的虫草可通过上调T辅助细胞1(Th1)相关细胞因子,下调Th2相关细胞因子,减少嗜酸粒细胞等炎症细胞渗出,抑制哮喘的慢性气道炎症,并与糖皮质激素具有协同作用.     

免疫治疗对支气管哮喘小鼠树突细胞共刺激分子的影响

目的应用卵白蛋白(OVA)建立特异性免疫治疗小鼠模型,探讨特异性免疫治疗对支气管哮喘(简称哮喘)小鼠树突细胞(DC)表面分子CD80、CD86表达的影响。方法120只BALB/c小鼠按随机数字表法分为哮喘模型组(A组)40只:用0.1%OVA 10μg连续腹腔注射(共70μg)及1%OVA雾化吸入(共300 mg);免疫治疗模型组(B组)40只:用与A组同剂量的OVA致敏和激发,同时连续尾根部皮下注射OVA 1 mg;对照组(C组)40只:以磷酸盐缓冲液代替OVA,其余同A组。留取各组肺组织切片,经苏木精-伊红(HE)染色观察炎症反应;用酶联免疫吸附测定(ELISA)法检测血清OVA特异性免疫球蛋白IgE(sIgE)及脾脏T淋巴细胞中白细胞介素2(IL-2)和IL-4的分泌。分离各组小鼠脾脏DC,用流式细胞仪检测其表面CD80、CD86分子表达。分离正常小鼠脾脏T淋巴细胞,与上述各组DC共培养;用ELISA法检测T淋巴细胞IL-4、IL-5的分泌量;用3H-胸腺嘧啶核苷(3H-TdR)掺入法检测其增殖反应。结果(1)B组小鼠肺组织中支气管及血管周围以大量淋巴细胞和嗜酸粒细胞为主的炎性细胞浸润明显轻于A组,但并未完全消失;A组血清sIgE吸光度(A)值为712±129,B组为124±59,C组为20±13,A、C组间比较差异有统计学意义(P<0.05),B、C组比较差异无统计学意义(P>0.05)。B组T淋巴细胞分泌IL-2、IL-4水平分别为(8±3)、(8.4±4.3)pg/m l,A组分别为(22±8)、(32.4±12.1)pg/m l,C组分别为(6±4)、(5.1±1.1)pg/m l,A、B两组比较差异有统计学意义(P<0.05),B、C组间比较差异无统计学意义(P>0.05);(2)B组DC表面CD86、CD80阳性表达率分别为58.23%、95.63%,A组分别为77.59%、96.98%,C组分别为77.37%、77.84%;(3)与B组DC共培养的正常小鼠T淋巴细胞体外经OVA刺激后,IL-4、IL-5水平分别为(10.8±2.3)、(18.8±3.8)pg/m l,A组分别为(17.3±4.7)、(35.7±7.9)pg/m l,C组分别为(5.7±2.7)、(11.0±2.2)pg/m l,A、B两组比较差异有统计学意义(P<0.05),B、C组间比较差异无统计学意义(P>0.05);B组DC与正常小鼠T淋巴细胞共培养时,刺激指数(SI)为3.8±0.7,A组为11.5±3.2,C组为5.8±1.5,A、B组间比较差异有统计学意义(P<0.05);B、C组间比较差异无统计学意义(P>0.05)。结论建立了OVA特异性免疫治疗小鼠模型;DC表面CD86分子表达的下调可能是OVA特异性免疫治疗诱导T淋巴细胞功能丧失的机制之一。     

Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma

The clinical effects of treatment with beta-adrenoceptor (beta-AR) agonists and antagonists in heart failure vary with duration of therapy, as do the effects of beta-AR agonists in asthma. Therefore, we hypothesized that chronic effects of "beta-blockers" in asthma may differ from those observed acutely. We tested this hypothesis in an antigen (ovalbumin)-driven murine model of asthma. Airway resistance responses (Raw) to the muscarinic agonist methacholine were measured by using the forced oscillation technique. In comparison with nontreated asthmatic mice, we observed that: (i) The beta-AR antagonists nadolol or carvedilol, given as a single i.v. injection (acute treatment) 15 min before methacholine, increased methacholine-elicited peak Raw values by 33.7% and 67.7% (P < 0.05), respectively; when either drug was administered for 28 days (chronic treatment), the peak Raw values were decreased by 43% (P < 0.05) and 22.9% (P < 0.05), respectively. (ii) Chronic treatment with nadolol or carvedilol significantly increased beta-AR densities in lung membranes by 719% and 828%, respectively. (iii) Alprenolol, a beta-blocker with partial agonist properties at beta-ARs, behaved as a beta-AR agonist, and acutely reduced peak Raw value by 75.7% (P < 0.05); chronically, it did not alter Raw. (iv) Salbutamol, a beta-AR partial agonist, acutely decreased peak Raw by 41.1%; chronically, it did not alter Raw. (v) None of the beta-blockers produced significant changes in eosinophil number recovered in bronchoalveolar lavage. These results suggest that beta-AR agonists and beta-blockers with inverse agonist properties may exert reciprocating effects on cellular signaling dependent on duration of administration.     

法舒地尔对支气管哮喘小鼠肺组织Rho激酶-1表达及气道炎症的影响

目的 观察Rho激酶-1抑制剂法舒地尔对支气管哮喘(简称哮喘)小鼠肺组织Rho激酶-1表达及气道炎症的影响,探讨Rho激酶-1在哮喘气道炎症中的作用机制.方法 将24只BalB/c小鼠采用随机数字表法分为对照组、哮喘组和干预组,每组8只.哮喘组、干预组小鼠分别给予卵清白蛋白(OVA)致敏和激发.每次雾化前1 h,干预组给予法舒地尔(10 mg/kg)腹腔注射.末次激发后收集BalF,离心后计数细胞总数及嗜酸粒细胞(EOS)数量.ELISA法测定BalF上清液中嗜酸粒细胞趋化因子(Eotaxin)、白细胞介素(IL)-5和IL-13水平.肺组织HE染色.采用逆转录PCR和免疫组织化学测定各组小鼠肺组织中Rho激酶-1 mRNA和蛋白的表达水平.结果 (1)哮喘组BalF中细胞总数及EOS数量分别为(1.45±0.12)× 10~9/L和(0.52 ±0.06)× 10~9/L,明显高于对照组[分别为(0.58±0.06)×10~9/L和(0.01±0.01)×10~9/L](q值分别为25.909和35.002,均P＜0.01)和干预组[分别为(0.89 ±0.09)×10~9/L和(0.20±0.04)×10~9/L](q值分别为16.676和21.537,均P＜0.01).(2)哮喘组Eotaxin、IL-5及IL-13水平分别为(45±8)ng/L、(157 ±23)ng/L和(429±46)ng/L,明显高于对照组[分别为(10 ±3)ng/L、(26±6)ng/L和(126 ±20)ng/L](q值分别为18.246、23.009、25.826,均P＜0.01);干预组分别为(20±5)ng/L、(57 ±14)ng/L和(254±28)ng/L,明显低于哮喘组(q值分别为13.119、17.503、8.449,均P＜0.01).(3)对照组小鼠气道周围无炎症细胞浸润,哮喘组小鼠气道黏膜水肿,气道壁及管周有大量以EOS为主的炎症细胞浸润,干预组气道炎症反应较哮喘组减轻.(4)哮喘组肺组织Rho激酶-1 mRNA和蛋白的表达水平明显高于对照组(q值分别为25.614和8.156,均P＜0.01),干预组Rho激酶-1 mRNA和蛋白表达水平低于哮喘组(q值分别为20.379和4.135,均P＜0.01).(5)Rho激酶-1 mRNA表达量与BalF中EOS数量、Eotaxin、IL-5和IL-13水平呈正相关(r值分别为0.709、0.600、0.613、0.650,均P＜0.01).结论 Rho激酶-1参与过敏原诱导的哮喘小鼠气道炎症的发生,应用法舒地尔抑制其表达和活性可能改善哮喘气道炎症.     

Vascular remodeling is airway generation-specific in a primate model of chronic asthma

RATIONALE: Changes in the density of bronchial vessels have been proposed as a part of airway remodeling that occurs in chronic asthma. OBJECTIVES: Using an established nonhuman primate model of chronic allergic asthma, we evaluated changes in vascular density as well as the contribution of bronchial epithelium to produce vascular endothelial growth factor (VEGF). METHODS: Eight juvenile rhesus macaques were divided into two groups of four. One group was exposed to 11 cycles of aerosolized house dust mite allergen (HDMA), whereas the other was exposed to filtered air. Bronchial wall vasculature was identified using an immunohistochemical approach, and vascular density was quantified stereologically. A semiquantitative polymerase chain reaction approach was used to estimate VEGF splice variant gene expression at discrete airway generations. Cell culture of primary tracheal epithelial cells with varying concentrations of HDMA was used to quantify the direct contribution of the epithelium to VEGF production. RESULTS: Bronchial vascular density was increased at mid- to lower airway generations, which was independent of changes in the interstitial compartment. The VEGF121 splice variant was significantly increased at lower airway generations. VEGF protein increased in a dose-dependant fashion in vitro primarily by an increase in VEGF121 gene expression. CONCLUSION: This study highlights that increased vascular density in an animal model of chronic allergic asthma is airway generation specific and associated with a unique increase of VEGF splice variant gene expression. Airway epithelium is the likely source for increased VEGF.     

Thymic stromal lymphopoietin contribution to the recruitment of circulating fibrocytes to the lung in a mouse model of chronic allergic asthma

Objective: Fibrocyte localization to the airways and thymic stromal lymphopoietin (TSLP) overexpression in the lung are features of severe asthma. The aim of this study was to determine whether TSLP contributes to fibrocyte trafficking and airway remodeling in a mouse model of allergic asthma. Methods: We established a chronic asthma animal model by administering house dust mite (HDM) extracts intranasally for up to 5 consecutive weeks. Mouse anti-TSLP monoclonal antibody (mAb) was given intraperitoneally starting the 4^th week. Fluorescence-labeled CD34/collagen I (Col I)-dual-positive fibrocytes were examined by confocal microscopy. The level of TGF-β1 in the bronchoalveolar lavage (BAL) fluid was determined by ELISA. Results: We found significantly increased levels of TSLP and TGF-β1 in the lung of the mice subjected to repeated allergen exposure, which was accompanied by increased number of fibrocytes in the sub-epithelial zone and the BAL fluid. However, blocking TSLP markedly decreased the production of TGF-β1, reduced the number of fibrocytes and subsequently prevented alterations of both airway and vascular structures. Conclusions: Our data suggested that TSLP might function in airway remodeling by promoting circulating fibrocyte recruitment to the lung in the mice subjected to chronic allergen exposure. These results provide a better rationale for targeting the interaction between TSLP and fibrocytes as a therapeutic approach for chronic allergic asthma.     

粉螨性小鼠哮喘模型的建立与评估

目的探讨采用椭圆食粉螨提取浸液建立C57BL/6小鼠哮喘模型的方法。方法 45只C57BL/6小鼠随机分成3组:PBS阴性对照组、卵清蛋白(OVA)阳性对照组、椭圆食粉螨(Ale o)哮喘模型组。用酶联免疫吸附试验(ELISA)检测支气管肺泡灌洗液(BALF)、脾细胞培养上清液中IL-4、IL-17和IFN-γ的含量,计数BALF中细胞总数并分类,同时切取小鼠未灌洗侧肺组织进行病理学观察。结果 OVA阳性对照组、Ale o模型组小鼠脾细胞上清和BALF中IL-4、IL-17及IFN-γ含量与PBS阴性对照组相比,差异均具有统计学意义(P<0.05或P<0.01);OVA阳性对照组、Ale o模型组小鼠BALF中细胞总数及各类细胞数与PBS阴性对照组相比,差异有统计学意义(P<0.05或P<0.01);小鼠未灌洗侧肺组织病理学观察显示,OVA阳性对照组和Ale o模型组小鼠肺组织可见大量炎症细胞浸润,以嗜酸性粒细胞、淋巴细胞及巨噬细胞为主。结论用椭圆食粉螨提取浸液建立的C57BL/6小鼠哮喘模型具有过敏性哮喘的主要特征。     

Neurobehavioral alterations in a mouse model of chronic partial sleep deprivation

Metabolic Brain Disease - The night shift paradigm induces a state of chronic partial sleep deprivation (CPSD) and enhances the vulnerability to neuronal dysfunction. However, the specific neuronal...     

Optimizing inhaled corticosteroid therapy in children with chronic asthma

Asthma is the most common chronic illness among children, and inhaled corticosteroids (ICS) are the most effective long-term therapy available for suppressing airway inflammation in persistent asthma. While the primary aim of ICS therapy is good efficacy with minimal side effects, early diagnosis and treatment of asthma can also improve asthma control and normalize lung function, and may prevent irreversible airway injury. Poor patient compliance is a major barrier to treatment. Simplified dosing regimens (e.g., once-daily administration), good inhaler technique, and education of the patient/caregiver should improve patient compliance. Concerns over ICS therapy are often based on the potential for systemic effects associated with oral corticosteroids (e.g., effects on bone mineral density, or growth suppression in children). Since adverse events are associated with high doses of ICS, the dose in all patients should be titrated to the minimum effective dose required to maintain control. Optimal distribution of an ICS in the lungs rather than the systemic compartment is affected by several factors, including the drug's pharmacokinetic profile, inhaler type, inhaler technique, and drug particle size. For young patients unable to use a dry-powder inhaler or pressurized metered-dose inhaler, a nebulizer facilitates drug delivery through passive inhalation; ICS therapy in the form of budesonide inhalation suspension can be given to children with persistent asthma from 12 months of age. In conclusion, selecting a drug with good efficacy and minimal side effects, such as budesonide, together with an easy-to-use delivery system and ongoing patient/caregiver education, is important in optimizing ICS therapy for children with persistent asthma.     

Efficacy of sulphasalazine on lung histopathology in a murine model of chronic asthma

Sulphasalazine is a specific inhibitor of nuclear factor kappa B (NF-kappa B) which plays a key role in asthma. To determine the impact of sulphasalazine in the treatment of chronic asthma, BALB/c mice were sensitized and challenged with ovalbumin. Mice with experimentally induced asthma in group I received saline, group II sulphasalazine 200 mg/kg, group III sulphasalazine 300 mg/kg, and group IV dexamethasone 1 mg/kg intraperitoneally once a day in the last 7 days of the challenge period. Histological findings of the airways were evaluated by light and electron microscopies. Dexamethasone and sulphasalazine in both doses significantly improved all airway histopathologic parameters of asthma except numbers of goblet cells. Both doses of sulphasalazine improved thicknesses of basement membrane better than dexamethasone. Dexamethasone reduced the number of mast cells better than sulphasalazine (200 mg/kg). Further studies are needed to evaluate the efficacy of sulphasalazine in the treatment of asthma.     

不同剂量虫草活力素对大鼠支气管哮喘模型慢性气道炎症的作用机制研究

目的对不同剂量虫草活力素（简称虫草）在大鼠支气管哮喘（简称哮喘）模型慢性气道炎症中的抑制作用及相关机制进行初步探讨。方法Wister大鼠,随机分为对照组、单纯模型组、虫草20mg／kg、50mg／kg组、布地奈德（BUD）组及BUD联合虫草素干预组。卵蛋白致敏建立大鼠哮喘模型后给予药物干预8周,对各组支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）进行细胞分类计数及观察肺组织的病理变化,同时应用双抗体夹心ABC—ELISA法测定血清和BALF的哮喘相关细胞因子水平。结果与单纯模型组比较,虫草两种剂量治疗组均降低慢性哮喘大鼠BALF的细胞总数和嗜酸粒细胞数,差异有统计学意义（P〈0．05）,并呈剂量相关性;HE染色显示大剂量虫草、BUD治疗组及联合用药组较单纯模型组炎症细胞浸润、平滑肌肥厚及黏膜肺组织水肿等炎症表现明显减轻;较单纯模型组,虫草治疗组血清及BALF的白介素4（IL-4）、IL-14水平下降,干扰素γ升高,差异有统计学意义（Pd0．05）,并呈剂量相关性。结论 一定剂量的虫草可通过上调T辅助细胞1（Th1）相关细胞因子,下调Th2相关细胞因子,减少嗜酸粒细胞等炎症细胞渗出,抑制哮喘的慢性气道炎症,并与糖皮质激素具有协同作用。