S-Allyl cysteine reduces eosinophilic airway inflammation and mucus overproduction on ovalbumin-induced allergic asthma model

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma.     

Genipin inhibits allergic responses in ovalbumin-induced asthmatic mice

Genipin is a natural compound isolated from the fruit of Gardenia jasminoides with various pharmacological effects. In this study, we investigated whether genipin effectively alleviates allergic responses in a murine model of ovalbumin (OVA)-induced asthma. The mice were administered an intraperitoneal injection of OVA on day 0 and 14 to boost the immune response; genipin was then administered from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was determined on day 24 by plethysmography. Genipin significantly reduced the inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic mice. In histology, genipin significantly decreased airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA-induced increases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic mice. Overall, genipin effectively alleviated the asthmatic inflammatory response in an OVA-induced asthmatic model. Therefore, our results suggest that genipin has therapeutic potential for treating asthma.     

雷帕霉素对哮喘小鼠气道重塑的影响

目的利用雷帕霉素探讨哺乳动物雷帕霉素靶蛋白(mTOR)在支气管哮喘小鼠气道重塑中的作用机制。方法30只♂清洁级BABL/c小鼠,随机数字表法分为3组,每组10只,分别为生理盐水对照组、卵蛋白(OVA)哮喘组、雷帕霉素治疗组。在末次激发24 h后所有小鼠取左肺组织行苏木精-伊红(HE)染色,PAS染色及mTOR免疫组织化学染色。分别用酶联免疫吸附法(ELISA)和Western blot检测支气管肺泡灌洗液(BALF)中IL-4、IL-5、IL-13含量以及右肺组织mTOR蛋白表达。应用小鼠肺功能仪检测气道阻力的变化。结果哮喘模型组小鼠与对照组相比较BALF中IL-4、IL-5、IL-13水平增高;肺组织mTOR蛋白表达水平明显高于对照组(P<0.01)。雷帕霉素治疗组与哮喘模型组相比较BALF中IL-4、IL-5、IL-13含量及肺组织mTOR表达水平均降低,差异具有显著性(P<0.05)。结论雷帕霉素可抑制哮喘小鼠气道重塑的发生,其机制有可能是通过阻断mTOR信号通路而实现的。     

Anti-inflammatory effect of amurensin H on asthma-like reaction induced by allergen in sensitized mice

AIM: To explore the anti-inflammatory effects of amurensin H on asthma-like reaction induced by allergen in sensitized mice. METHODS: BALB/c mice were sensitized by ovalbumin (OVA, ip) on d 0 and d 14 and challenged with 1% OVA on d 18 to 22. Mice developed airway eosinophilia, mucus hypersecretion, and elevation in cytokine levels. Mice were administered amurensin H orally at the doses of 49, 70, or 100 mg/kg once every day from d 15 to the last day. Bronchoalveolar lavage fluid (BALF) were collected at 24 h and 48 h after the last OVA challenge. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in BALF were measured using ELISA method. Differential cell counts of macrophages, lymphocytes, neutrophils and eosinophils were performed in 200 cells per slide (one slide per animal). Lung tissue sections of 6-mum thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration, mucus production, and tissue damage. RESULTS: Oral administration of amurensin H significantly inhibited OVA-induced increases in total cell counts, eosinophil counts, and TNF- alpha, IL-4, IL-5 and IL-13 levels in BALF. In addition, amuresin H dramatically decreased OVA-induced lung tissue damage and mucus production. CONCLUSION: Amurensin H may have therapeutic potential for the treatment of allergic airway inflammation.     

Tiarellic acid attenuates airway hyperresponsiveness and inflammation in a murine model of allergic asthma

Asthma is a persistent inflammatory disease characterized by airway obstruction and hyperresponsiveness in association with airway inflammation. In the current research, we studied the anti-inflammatory and anti-asthmatic effects of tiarellic acid (TA) isolated from Tiarella polyphylla, based on asthmatic parameters, such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness (AHR), reactive oxygen species (ROS) and mucus hypersecretion, in an ovalbumin (OVA)-sensitized/challenged mouse model. TA significantly inhibited increases in IgE, levels of ROS and T helper cytokines, such as interleukin (IL)-4, IL-5, TNF-α, and IL-13, in bronchoalveolar lavage fluid (BALF), and effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. In addition, we found that administration of TA attenuated ovalbumin-induced increases in NF-κB activity in lungs. The efficacy of TA was comparable to that of montelukast, a currently available anti-asthmatic drug. Our results support the utility of TA as a herbal medicine for asthma treatment and may have application in the development of anti-inflammatory and anti-asthmatic drugs.     

Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice

Pinocembrin, one of the primary flavonoids in propolis, possesses many biological activities, including anti-inflammation, anti-oxidation and immunoregulation. This study aimed to evaluate whether pinocembrin could attenuate ovalbumin (OVA)-induced allergic airway inflammation in mice and to explore the possible mechanism. BALB/c mice sensitized and challenged with OVA were administered intraperitoneally with pinocembrin. Airway inflammation and airway hyperresponsiveness were examined. T-helper type (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E (IgE) in serum were determined. The activation of nuclear factor kappa B (NF-κB) p65 were also measured. Our results showed that pinocembrin resulted in significant inhibition of pathophysiological signs of allergic asthma, including increased pulmonary eosinophilia infiltration, mucus hypersecretion and airway hyperresponsiveness (AHR). Treatment with pinocembrin significantly reduced Th2 cytokines interleukin (IL)-4, IL-5 and IL-13 in BALF, and OVA-specific IgE in serum. Moreover, pinocembrin treatment suppressed phosphorylation of inhibitor-κBα (IκBα) and NF-κB subunit p65 activation in lung tissue of OVA-sensitized mice. These data suggest that pinocembrin may inhibit allergic airway inflammation, and providing potential benefits in the treatment of inflammatory disease.     

基于IL-13/STAT6信号通路研究祛风宣痹方对哮喘气道黏液高分泌的影响

目的：探讨祛风宣痹方对哮喘小鼠气道黏液分泌及IL-13/STAT6信号通路的影响。方法：采用卵清蛋白（OVA）致敏建立小鼠哮喘模型。将24只Balb/c雌性小鼠随机分为对照组、哮喘组、祛风宣痹方组，祛风宣痹方组给予祛风宣痹方治疗，对照组和哮喘组给予等量生理盐水灌胃。采用肺组织HE染色、PAS染色观察肺组织病理形态变化以及气道黏液分泌，免疫组化实验观察黏蛋白MUC5AC、p-STAT6蛋白表达情况，ELISA实验检测小鼠血清中IL-13的含量。IL-13处理A549细胞模拟黏蛋白分泌病理模型（IL-13组），再加入祛风宣痹方进行干预（IL-13+祛风宣痹方组）；采用免疫荧光技术检测A549细胞中MUC5AC和p-STAT6的表达情况。结果：体内实验发现，与哮喘组相比，祛风宣痹方组小鼠肺组织中炎症细胞浸润及黏液高分泌情况均有明显改善，气道表面细胞MUC5AC、p-STAT6蛋白表达有所降低（P < 0.05）；小鼠血清中IL-13含量也明显减少（P < 0.01）。体外实验发现，与对照组相比，IL-13组A549细胞中MUC5AC及p-STAT6蛋白表达明显升高（P < 0.01），而IL-13+祛风宣痹方组细胞中MUC5AC及p-STAT6蛋白表达相对于IL-13组呈现明显下降趋势（P < 0.05）。结论：祛风宣痹方可减轻哮喘气道黏液高分泌，其作用机制可能与抑制IL-13/STAT6信号通路相关。     

Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosterone and catecholamines

This study investigates the role of adrenal-derived catecholamines and corticosterone on the inhibition by rolipram, a phosphodiesterase (PDE)-4 inhibitor, of pulmonary eosinophilia and airway hyperresponsiveness (AHR) in allergic mice. The following experimental groups were studied in mice sensitized and challenged with ovalbumin (OVA): normal, adrenalectomized, propranolol (beta-adrenoceptor antagonist) and metyrapone (corticosterone synthesis inhibitor) treated. These interventions were studied both in the absence and in the presence of rolipram. Eosinophil numbers in the bronchoalveolar lavage (BAL) and AHR to methacholine were measured 24 h after OVA challenge. Treatment of sensitized mice with rolipram (0.3 - 10 mg kg(-1), p.o.), inhibited pulmonary eosinophilia and the AHR to methacholine in OVA-challenged mice. Adrenalectomy increased the number of eosinophils in the BAL of OVA-challenged mice but had no effect on AHR to methacholine. Adrenalectomy attenuated both the rolipram-induced inhibition of BAL eosinophilia and AHR to methacholine in OVA challenged mice. Propranolol (10 mg kg(-1), p.o.) had no effect on the inhibition of eosinophilia by rolipram but attenuated the inhibition of AHR to methacholine in OVA challenged mice. On the other hand, metyrapone (10 mg kg(-1), p.o.) attenuated the inhibition of eosinophilia by rolipram but had no effect on the inhibition of AHR to methacholine in OVA challenged mice. Metyrapone-treatment alone increased the number of eosinophils in the BAL of OVA-challenged mice. These results identify an important role for adrenal-derived catecholamines and corticosterone on the inhibition of pulmonary eosinophilia and AHR by rolipram in allergic mice.     

哮喘小鼠气道上皮杯状细胞增生模型

目的建立一种新的小鼠气道上皮杯状细胞增生和粘液高分泌模型。方法用卵白蛋白加氢氧化铝凝胶皮下注射致敏小鼠,d 10腹腔注射重复致敏1次,然后从第1次致敏后d 15~21每天用卵白蛋白雾化吸入攻击1次。检测AB-PAS染色的支气管上皮杯状细胞数目,HE染色的肺组织嗜酸性粒细胞浸润和支气管灌洗液中的炎症细胞数目,并用已知有效药物和未知受试药物验证此模型。结果卵白蛋白致敏和攻击的小鼠呈现明显的支气管上皮杯状细胞增生,管腔内黏液增多,肺组织嗜酸性粒细胞浸润和支气管灌洗液中的炎症细胞数目增加,这些病理改变可被地塞米松和小鼠IL-12质粒抑制。结论这一模型有助于筛选抗黏膜高分泌的新药和研究气道黏膜高分泌的病理机制。     

Progress in allergy signal research on mast cells: the role of histamine in goblet cell hyperplasia in allergic airway inflammation - a study using the Hdc knockout mouse

Although histamine is a central mediator in the immediate allergic reaction, its role in goblet cell hyperplasia in the airway of asthma is not completely understood. This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc(-/-) mice) with allergic airway inflammation. Wild-type and Hdc(-/-) C57BL/6 mice were sensitized with ovalbumin (OVA). After two-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials in BALF were analyzed. The mRNAs level of MUC5AC and Gob-5 gene were quantitatively determined. The number of eosinophils in BALF increased in both the wild-type mice and Hdc(-/-) mice; however, their ratio in Hdc(-/-) mice was significantly lower than that in the wild-type mice. The mRNA levels of Gob-5 and MUC5AC and the ratio of the goblet cells in the airway epithelium were significantly increased in Hdc(-/-) mice exposed to OVA compared to the wild-type mice under the same condition. These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.     

Homoegonol attenuates the asthmatic responses induced by ovalbumin challenge

Homoegonol is a lignan derived from styraxlignolide A, which was isolated from Styrax japonica, a medicinal plant widely used for treatment of inflammatory diseases in Korea. We investigated the efficacy of homoegonol for the treatment of allergic asthma using an ovalbumin (OVA)-induced murine asthma model. The mice were sensitized through intraperitoneal injections of OVA on days 0 and 14. On days 21, 22 and 23 after the initial OVA sensitization, the mice were received OVA airway challenge. Homoegonol was administered by oral gavage at a dose of 30 mg/kg 1 h prior to the OVA challenge. The homoegonol-treated mice exhibited reduced inflammatory cell counts and Th2 cytokines in BALF, AHR, and IgE in the serum compared with the OVA-sensitized/challenged mice. The histological analysis of the lung tissue revealed that the administration of homoegonol attenuated the airway inflammation and the mucus overproduction in airway epithelial lesions induced by OVA through a reduction in expression of inducible nitric oxide synthase and matrix metalloproteinase-9. These findings indicate that homoegonol effectively suppresses the asthmatic responses induced by OVA challenge and suggests that homoegonol exhibits potential as therapeutic drug for allergic asthma.     

Aggravating effects of Asian sand dust on lung eosinophilia in mice immunized beforehand by ovalbumin

Asian sand dust (ASD) event may result in a significant influence on an asthmatic patient. However, for obvious reasons, there is no experimental study in which asthmatic patients are exposed to ASD. This study was undertaken to clarify the effects of ASD on lung eosinophiliain mice immunized beforehand by ovalbumin (OVA). CD-1 mice were instilled intratracheally with OVA four times at 2-week intervals. Simultaneous intratracheal administration of OVA and ASD (OVA + ASD sim) at the last OVA treatment or intratracheal administration with ASD 1 day before (OVA + ASD pre) /after (OVA + ASD post) the last OVA treatment was performed to investigate the effects of OVA and ASD exposure timing. The three kinds of treatment (OVA + ASD pre; OVA + ASD sim; OVA + ASD post) aggravated allergic lung inflammation and proliferation of goblet cells in the airway epithelium in mice, as evidenced by the cellular profile of bronchoalveolar lavage fluid (BALF) and pathological examination. As an overall trend, these changes were paralleled with the expression of Th2-associated effecter molecules and eosinophil relevant cytokine chimokines in BALF as well as the production of OVA-specific IgG1 compared with OVA treatment alone. OVA + ASD sim aggravated lung eosinophilia remarkably compared with the other treatments. The order of the potency of the aggravation was OVA+ASD pre < OVA+ASD post <OVA+ASD sim. These results indicate that ASD has a potent effect in activating lung eosinopilia in mice immunized beforehand by OVA. The simultaneous exposure of asthmatic patients to ASD and its antigen may have serious consequences for such individuals.     

Anti-asthmatic effect of schizandrin on OVA-induced airway inflammation in a murine asthma model

Asthma comprises a triad of reversible airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. Clinical and experimental findings have established eosinophilia as a sign of allergic disorders. In the present investigation, we evaluated the anti-asthmatic effects of schizandrin and its underlying mechanisms in an in vivo murine asthmatic model. To accomplish this, female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and examined for the following typical asthmatic reactions: increased numbers of eosinophils and other inflammatory cells in bronchoalveolar lavage fluid (BALF); production of Th1 cytokines (such as tumor necrosis factor (TNF)-α in BALF); production of Th2 cytokines (such as interleukin IL-4 and IL-5) in BALF; presence of total and OVA-specific immunoglobulins (Ig)E in serum; presence of oxidative stress; hyperplasia of goblet cells in the lung; and marked influx of inflammatory cells into the lung. Our results collectively show that schizandrin exerts profound inhibitory effects on accumulation of eosinophils into the airways and reduces the levels of IL-4, IL-5, IFN-γ, and TNF-α in BALF. Additionally, schizandrin suppresses the production of reactive oxygen species (ROS) in a dose-dependent manner, and inhibits goblet cell hyperplasia and inflammatory cell infiltration in lung tissue. Thus, schizandrin has anti-asthmatic effects, which seem to be partially mediated by reduction of oxidative stress and airway inflammation, in a murine allergic asthma model. These results indicate that schizandrin may be an effective novel therapeutic agent for the treatment of allergic asthma.     

Aggravating effects of Asian sand dust on lung eosinophilia in mice immunized beforehand by ovalbumin

Asian sand dust (ASD) event may result in a significant influence on an asthmatic patient. However, for obvious reasons, there is no experimental study in which asthmatic patients are exposed to ASD. This study was undertaken to clarify the effects of ASD on lung eosinophiliain mice immunized beforehand by ovalbumin (OVA). CD-1 mice were instilled intratracheally with OVA four times at 2-week intervals. Simultaneous intratracheal administration of OVA and ASD (OVA + ASD sim) at the last OVA treatment or intratracheal administration with ASD 1 day before (OVA + ASD pre) /after (OVA + ASD post) the last OVA treatment was performed to investigate the effects of OVA and ASD exposure timing. The three kinds of treatment (OVA + ASD pre; OVA + ASD sim; OVA + ASD post) aggravated allergic lung inflammation and proliferation of goblet cells in the airway epithelium in mice, as evidenced by the cellular profile of bronchoalveolar lavage fluid (BALF) and pathological examination. As an overall trend, these changes were paralleled with the expression of Th2-associated effecter molecules and eosinophil relevant cytokine chimokines in BALF as well as the production of OVA-specific IgG1 compared with OVA treatment alone. OVA + ASD sim aggravated lung eosinophilia remarkably compared with the other treatments. The order of the potency of the aggravation was OVA+ASD pre < OVA+ASD post 相似文献   

An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model

Phosphoinositide 3-kinase (PI3K) exhibits broad functional effects in immune cells. We investigated the role of PI3K in allergic airway inflammation using LY294002, a specific PI3K inhibitor, in a mouse asthma model. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and developed airway eosinophilia, mucus hypersecretion, elevation in cytokine levels, and airway hyperresponsiveness. Intratracheal administration of LY294002 significantly inhibited OVA-induced increases in total cell counts, eosinophil counts, and IL-5, IL-13, and eotaxin levels in bronchoalveolar lavage fluid. Histological studies show that LY294002 dramatically inhibited OVA-induced lung tissue eosinophilia and airway mucus production. In addition, LY294002 significantly suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. Western blot analysis of whole lung lysates shows that LY294002 markedly attenuated OVA-induced serine phosphorylation of Akt, a direct downstream substrate of PI3K. Taken together, our findings suggest that inhibition of PI3K signaling pathway can suppress T-helper type 2 (Th2) cytokine production, eosinophil infiltration, mucus production, and airway hyperresponsiveness in a mouse asthma model and may have therapeutic potential for the treatment of allergic airway inflammation.     

血红素氧合酶-1对哮喘小鼠模型IL-25和MUC5AC表达的影响

摘要：目的　探讨血红素氧合酶-1（HO-1）对哮喘小鼠气道炎症的调节作用及其机制。方法　将28只健康雌性Balb/c小鼠根据随机数字表法分为4组：对照组、哮喘组、血晶素组、福多司坦组,每组7只。哮喘组、血晶素组和福多司坦组小鼠于第1天和第14天腹腔注射20 μg卵清蛋白（OVA）+500 μg Al（OH）3+0.2 mL PBS致敏,于第25~28天每天雾化吸入1次OVA激发气道高反应制备小鼠哮喘模型,对照组以等量生理盐水替代,血晶素组致敏前1、2 d,致敏后12、13、23、24、27 d腹腔注射血晶素75 μmol/kg,福多司坦组分别于致敏前25、26、27 d灌胃给药福多司坦（200 mg/kg）,末次激发后24 h内处死小鼠并收集血液、肺组织。HE染色观察肺组织形态学改变,免疫组化检测肺组织黏蛋白5AC（MUC5AC）的表达,酶联免疫吸附测定（ELISA）法检测肺组织中MUC5AC和血清中白细胞介素（IL）-25的水平,并对MUC5AC和IL-25进行相关性分析。结果　哮喘组肺组织可见大量炎症细胞浸润、气管黏膜增厚、黏膜下水肿,血晶素组和福多司坦组可见少量炎症细胞浸润及渗出,病理改变较哮喘组轻。与对照组相比,哮喘组、血晶素组、福多司坦组MUC5AC和IL-25的表达水平明显升高（P＜0.05）;与哮喘组相比,血晶素组和福多司坦组MUC5AC和IL-25降低（P＜0.05）,且血晶素组较福多司坦组降低更明显（P＜0.05）。MUC5AC与IL-25的表达水平呈正相关（r=0.932,P＜0.01）。结论　HO-1可下调哮喘小鼠MUC5AC和IL-25的表达,减轻气道炎症和黏液高分泌。     

Involvement of PM2.5-bound protein and metals in PM2.5-induced allergic airway inflammation in mice

Abstract

Background: The aim of this study was to investigate the protein and trace element components of PM2.5 and their contribution to the allergic airway inflammation in BALB/c mice.

Methods: PM2.5, treated at high temperature and with a strong acid to hydrolyze any protein content and remove trace elements, was administered to BALB/c mice. Allergic airway inflammation was compared between the three groups (saline, pure PM2.5 and treated PM2.5) by evaluating airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cells, serum IgE, the mRNA of various cytokine (IL-4, IL-5, IL-13, eotaxin-1 and CXCL3), mucus protein mRNA (MUC5ac and MUC5b) and the filtration of inflammatory cells in the lung.

Results: The treatment of PM2.5 with a strong acid at a high temperature attenuated AHR, eosinophil percentage in BALF, mRNA levels of IL-13 and CXCL3 and peribronchial inflammation. On the contrary, the percentage of neutrophils in BALF, mRNA expression of MIP2α, EGFR, Nrf2, and TLR4 and 4-OH-2-nonenal levels in the lung was increased. Moreover, the treatment of the PM2.5 reduced PM2.5-bound proteins as well as the percentages of the trace elements in PM2.5 in the order Zn?>?Cu?> Pb?>?P?>?S?>?Mn?>?Fe?>?Ca?>?Ni, whereas the percentage of C, Si and Cl increased.

Conclusions: PM2.5 collected by of the cyclone system induced allergic airway inflammation in mice. PM2.5-bound proteins and acid-soluble metals may be involved in the pathogenesis of PM2.5-induced allergic airway inflammation.     

过氧化物酶体增殖体活化受体-γ对哮喘小鼠气道黏液的影响

目的:选用罗格列酮作为过氧化物酶体增殖体活化受体γ(PPARγ)的激动剂,探讨PPARγ对哮喘小鼠气道炎症和黏液的影响。方法:动物随机分为正常对照组、哮喘模型组和罗格列酮组,采用鸡卵清蛋白(Ova)致敏和激发制备小鼠哮喘模型。罗格列酮组予罗格列酮3mg·kg-1·d-1灌胃,对照组和模型组用同体积生理盐水代替。检测气管血管周围嗜酸粒细胞(Eos)数目、气管上皮杯状细胞增生指数和黏液储备指数、肺组织MUC5acmRNA的表达及MUC5ac蛋白的表达。结果:罗格列酮组气管血管周围Eos数目(169±s110)个·mm-2显著减少,气道杯状细胞增生指数及黏蛋白MUC5acmRNA的吸光度值分别为(25±16)个·mm-1,(0.83±0.06),和模型组比较差异有显著意义(P<0.05),黏液储备指数为(12±10)%,和模型组比较也有下降,但差异无显著意义。免疫组化显示罗格列酮组的MUC5ac阳性染色程度和正常对照组相似,和模型组比较阳性程度明显减轻。结论:PPARγ抑制哮喘小鼠气道Eos浸润和黏液高分泌。     

磷酸酰肌醇-3激酶抑制剂对小鼠气道炎症影响的实验研究

目的观察磷酸酰肌醇-3激酶（P13K）抑制剂LY294002对卵白蛋白诱导哮喘小鼠气道炎症的影响。方法Balb／c小鼠30只，采用随机数字表法分为3组，每组10只：LY294002处理组、卵白蛋白组、正常对照组。通过卵白蛋白多次腹腔注射致敏和反复雾化激发，建立哮喘小鼠模型。末次抗原激发后48h收集支气管肺泡灌洗液和骨髓标本，计数细胞总数和嗜酸性粒细胞，并行肺组织学检查。结果与卵白蛋白组比较，LY294002处理组支气管肺泡灌洗液中细胞总数及嗜酸性粒细胞绝对数明显减少（P〈0．05）：肺组织中细支气管、血管周围嗜酸性粒细胞浸润得到控制，气道黏液分泌减少。结论P13K特异性抑制剂LY294002对卵白蛋白致敏的哮喘小鼠气道炎症具有抑制作用。     

4-Carvomenthenol ameliorates the murine combined allergic rhinitis and asthma syndrome by inhibiting IL-13 and mucus production via p38MAPK/NF-κB signaling pathway axis

The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5–50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome.