• 동의생리병리학회지
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• 제23권2호
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• pp.343-350
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• 2009

This study aimed to evaluate the anti-asthmatic effects of Samjajihwang-tang (SJT) using OVA-induced asthmatic mice model. Asthmatic mice model was conducted by repeated challenge of OVA using C57BL/6 mice. Each group was treated with distilled water, SJT (400 mg/kg and 200 mg/kg) extract or cyclosporin A (10 mg/kg) for the later 8 weeks, Penh (plethysmography and enhanced pause), immune cells subpopulation, eotaxin, IL-5, TNF-${\alpha}$, Anti-OVA-lgE in BALF (bronchoalveolar lavage), and lung tissue was analyzed, No cytotoxicity of SJT was shown on hFCs (human fibroblast cells). Administration of SJT significantly decreased Penh levels comparing to control group. SJT treatment significantly ameliorated the increase of total cells number and eosinophil including of immune cell subpopulation of $CD3^+/CD69^+$, $CCR3^+$, $B220^+/CD22^+$, $B220^+/CD45^+$, and $B220^+/lgE^+$ cells in BALF comparing to control group. Eotaxin, IL-5, TNF-${\alpha}$, and Anti-OVA-lgE level in BALF were significantly decreased by SJT treatment too. Histopathological finding verified the improvement of infiltration of inflammatory cells and collagen tissue in the SJT groups comparing to control group. These results strongly suggest that SJT would be a effective candidate for herbal-originated anti-asthmatic drug. However, this drug should be further studied for characterization of the accurate action and underlying mechanisms using variant disease model in the future.

• Journal of Microbiology
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• 제43권1호
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• pp.11-16
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• 2005

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.

• 한방안이비인후피부과학회지
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• 제20권3호
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• pp.107-117
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• 2007

Objective : Kumsoouyukkun-joen extract(KSE) has been used treating asthma for a long time in korea. In the present study, I examined the effects of KSE on the ovalbumin(OVA)-induced airway hyper-reactivity(AHR). Methods : To examine the effects of KSE on asthma, mice were sensitized with $100{\mu}g$ of OVA and 1 mg of aluminum potassium sulfate(Alum; Sigma)intraperitoneally on day 0 and 7. On day 14, mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 hrs after the last challenge. To examine severity of AHR, I examined eosinophil population and cytokine production in bronchoaveloar lavage fluid(BALF) and stained with hematoxylin and eosin in lung and also measured enhanced pause(Penh) in AHR from mice. Results and Conclusion : KSE potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR. KSE also inhibited cytokines production such as IL-4, IL-5 in BALF. Furthermore, KSE inhibited percentage of eosinophil in BALF. These results suggest that KSE may be beneficial oriental medicine for AHR.

• 동의생리병리학회지
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• 제23권3호
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• pp.590-598
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• 2009

The purpose of this research is to evaluate the effect of Mahaenggamseok-tang-gagambang (MGTG) on airway hyper- responsiveness (AHR), immune cells, cytokines and lung tissue in OVA-induced asthmatic mice. C578L/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (3times a week) for asthma sensitization and challenge. Two experimental groups were treated with different concentrations of MGTG (400 mg/kg and 200 mg/kg) extract and cyclosporin A (10 mg/kg) for the later 8 weeks. Enhanced pause (Penh) levels were measured by whole body plethysmography. Immune cells were analyzed by flow cytometer in peripheral blood monocyte cell (PBMC) and lung cells. The IL-1b, IL-12, IFN-${\gamma}$, OVA-lgE, IL-4, IL-5, TNF-${\alpha}$ were analyzed by ELISA kit in serum and splenocyte+a-cCDS/a-CD28. Enhanced pause (Penh) levels of the MGTG groups (400 mg/kg and 200 mg/kg) were decreased significantly compared with that of control group. The numbers of MGTG groups (400 mg/kg and 200 mg/kg) on lung total cells were decreased significantly compared with that of control group. The numbers of MGTG groups (400 mg/kg and 200 mg/kg) on $CD3^+/CD69^+$, $B220^+/CD22^+$, $B220^+/CD23^+$, $B220^+/lgE^+$, $CCR3^+$ cells were decreased significantly compared with that of control group. The number of MGTG group (400 mg/kg) on $CD3^+/CD49b^+$ cells was decreased significantly compared with that of control group. The level of MGTG groups (400 mg/kg and 200 mg/kg) on IL-4, IL-5, IL-12, TNF-${\alpha}$, OVA-lgE were decreased significantly compared with that of control group. The level of MGTG group (400 mg/kg) on IL-1b, IL-1S, OVA-lgE were decreased significantly compared with that of control group. These results demonstrate that MGTG could be a desirable alternative therapy for allergic asthma by inhibiting the expression of immune cells, the activation of inflammatory mediator.

• Tuberculosis and Respiratory Diseases
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• 제57권5호
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• pp.425-433
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• 2004

연구배경 : 경구면역관용 유도는 4주 이내의 급성천식모델에서 알레르기 염증반응을 효과적으로 억제하는 것으로 알려져 있다. 하지만 경구면역관용 유도가 4주 이상 지속되는 만성천식모델에서도 알레르기 염증반응을 효과적으로 억제할 수 있는 지에 대해서는 아직 불확실하다. 본 연구에서는 8주 동안 지속되는 만성천식모델을 이용하여 경구면역관용 유도가 알레르기 염증반응 및 기도재형성에 어떤 영향을 미치는 지를 관찰하였다. 방 법 : 5주된 암컷 BALB/c 마우스에 ovalbumin(OVA)을 복강 내로 투여하여 감작시킨 후, 6주 동안 주 2회 OVA를 반복 흡입시킴으로써 만성천식모델을 만들었다. 경구면역관용은 감작시키기 전에 OVA를 경구 투여함으로써 유도하였으며, 저용량 군(OVA 1 $mg/day{\times}6$일)과 고용량 군(OVA 25 $mg/day{\times}1$일)으로 나누었다. 기도과민성은 농도별 메타콜린 흡입에 따른 enhanced pause (penh) 값의 변화로 평가하였으며, 기관지폐포세척액 내의 염증세포수를 측정하고 IL-13, IFN-${\gamma}$ 농도 및 혈청 내 OVA 특이 IgE, IgG1, IgG2a 농도를 ELISA로 측정하였다. 기도재형성 정도는 폐조직의 PAS 및 Masson's trichrome 염색으로 관찰하였다. 결 과 : 경구면역관용군은 천식군에 비해 penh 값, 기관지폐포세척액 내의 염증세포 수, IL-13 및 IFN-${\gamma}$ 농도, 혈청 내의 OVA 특이 IgE, IgG1 및 IgG2a 농도, 폐조직 술잔세포의 과다형성, 기저막하부의 섬유화 정도가 유의하게 감소되었다 (P<0.05). 결 론 : 알레르기 기관지천식모델에서 경구면역관용 유도는 8주까지 장기적으로 기도과민성, 염증반응 및 기도재 형성을 억제하였으며, 그 기전에는 항원 특이 면역글로불린과 Th1 및 Th2 시토카인들에 대한 억제작용이 중요한 역할을 하는 것으로 추측되었다.

• 한방안이비인후피부과학회지
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• 제28권4호
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• pp.74-91
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• 2015

Background and Objective : Asthma is a chronic inflammatory disease at the mucosa and is associated with excess production of Th2 cytokine and eosinophil accumulation in lung.Gamchomahwang-tangextract(GME) is one of the well known prescription used in oriental medicine for treating asthma. This study was designed to compare the anti-asthmatic effect of GME according to the ratio of 2 compounds.Methods : To examine the effects of GME on asthma, mice were sensitized with 100 ㎍ of OVA and 1 ㎎ of aluminum potassium sulfate(Alum; Sigma) intraperitoneally on day 1 and 15. From day 22, mice were challenged on 3 consecutive days with 5% OVA. The anti-asthmatic effects of GME were evaluated by enhanced pause(Penh), bronchoalveolar lavage fluids (BALF), inflammatory cytokine production and genes expression, serum IgE production. and histological change in lung tissue. GMEⅠ consists of ES and GU in the proportion 2:1(300 ㎎/㎏ group), GMEⅡ consist of ES and GU in the proprtion 4:1(300 ㎎/㎏ group).Results : GMEⅠ,Ⅱ generally inhibited lung inflammation, inflammatory cells infiltration and cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and serum IgE level. GMEⅡ significantly reduced the cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and GMEⅠ decreased cytokine production of IL-4, IL-13 in BALF and gene expression of IL-4, IL-5 in Lung. GMEⅡ potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR(airway hyper-reactivity). Overall the results show that GMEⅡ has more effect on inhibiting production, gene expression of cytokine, serum IgE level and development of Penh than GMEⅠ. Consequently, GMEⅡ might be more effective than GMEⅠ at inhibiting allergic asthma on the OVA-induced mice model.Conclusion : These results indicate that GME has a deep inhibitory effects on airway inflammation and hyperresponsiveness in mice model of asthma and that suppression of IL-4, IL-5, IL-13 expression and decrease of IL-4, IL-5, IL-13 production in BALF might contribute this effect. Hence, the results indicate that GME might be useful herbal medicine of allergic asthma. As a result, GMEⅡ mght be superior to GMEⅠ in the aspect of anti-asthmatic effect on the OVA-induced mice model.

• 대한본초학회지
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• 제24권4호
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• pp.107-113
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• 2009

Objectives : This study was designed to investigate the effects of alcoholic fermentation beverage using pear, Bae Ro Mi In (BRMI) on airway hyperresponsiveness and immunoglobulin production in asthmatic mice Methods : We investigated the effects of BRMI on airway hyperresponsiveness by measurement of enhanced pause (Penh), and also investigated the effects on production levels of antigen specific antibody and subclasses such as IgG1, IgG2a and IgE by using ELISA methods. Prednisolone (PD, 5 mg/kg) was used as positive control. Results : Treatment with BRMI did not lowered airway hyperresponsiveness, but PD lowered significantly. Oral administration of BRMI lowered production level of ovalbumin (OVA) specific total antibody significantly. Especially, BRMI decreased IgE levels compared to non-treated control effectively. Treatment with PD lowered production levels of total antibody, IgG1 and IgE. Conclusions : These result suggest that BRMI can lower production levels of antigen specific total antibody and IgE in asthmatic mice. We also suggest that BRMI has the possibility to prevent or cure asthma through regulation of antigen specific antibody production.

• Tuberculosis and Respiratory Diseases
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• 제48권1호
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• pp.33-44
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• 2000

연구배경: 기관지천식은 기도의 과민성을 특징을 지닌 기도의 염증성 질환이며, 기관지천식에서의 기도 염종의 특성에 관한 연구는 기관지천식의 병인과 병태생리를 이해하는데 필수적이다. 본 연구의 목적은 백서에서 국내에서 개발된 일실 체용적 변동기록기을 이용하여 항원에 의한 반응을 관찰하여 기관지천식의 모델을 확립하고, 사람 기관지 천식과의 유사성을 알아보고자 백서의 기관지천식 모텔에서 기도의 염증을 관찰하여 항원에 의한 기도의 반응 양상에 따른 차이를 비교하고자 하였다. 대상 및 방법: 백서 30마리에 0.1mg의 난황을 피하로 주입하여 감작시키고, 감작후 14-16일 항원유발시험을 시행하여 각 10마리씩 3군으로 나누어 기도의 반응을 관찰하면서 1시간, 6-8시간, 24시간 후에 사망시켜 폐조직의 변화를 관찰하였다. 대조군 10마리는 감작군과 동일한 방법으로 항원을 흡입하고 1일 후에 사망시켰다. 기도반응은 동물용 일실 체용적 변동기록기를 사용하여 enhanced pause(Penh)를 지표로 측정하였다. 병리소견은 백서를 사망시켜 폐와 기관지를 절제한 후 Hematoxylin Eosin으로 염색하여 기관, 대기관지 및 소기관지 및 혈관주위에서 염증반응과 호산구 침윤을 관찰하였다. 결 과: 항원 유발시험을 시행한 20마리중 총 17마리(85%)에서 항원에 의한 기도의 수축반응을 보였다. 이들중 15 마리(75%)에서 조기반응을, 5 마리(25%)는 이중반응을 보였고 2마리(10%)는 후기반응만을 보였다. 항원 유발 후 기관, 대기관지, 소기관지와 혈관주 위에서의 염증반응은 1시간군, 6시간군, 1일군모두에서 대조군과 유의한 차이는 없었다(p>0.05). 항원유발시험후 호산구의 침윤은 1시간군과 대조군에서는 호산구의 침윤을 전혀 관찰할 수 없었으나, 6시간군은 5마리(50%)에서 호산구의 침윤을 관찰하였으며, 대조군과 유의한 호산구의 침윤을 관찰할 수 있었다(p<0.05). 조기반응과 후기반응을 관찰할 수 있었던 6시간군과 1일군에서 조기반응군(조기반응만을 보인 백서, n=10)과 후기반응군(이중반응과 후기반응만을 보인 백서, n=7) 에서 염증의 침윤은 모든 부위에서 유의한 차이는 없었다. 호산구의 침윤은 조기반응군에는 10마리중 4마리(40%)에서 $0.7{\pm}1.1$등급이었으며, 후기반응군은 7마리중 4 마리(57.1%)에서 $1.0{\pm}1.0$으로 높았으나, 통계적으로 유의하지는 않았다(p>0.05). 결 론: 백서의 기관지천식 모델에서 항원에 의한 기도의 수축 반응은 높고 반응률을 보였으나 기도의 염증 반응을 유발하지는 않으며, 호산구의 침윤도 미약하다고 생각된다. 그러므로 백서 기관지 천식모델은 항원에 의한 기도 반응의 연구에는 좋으나, 사랑의 만성 기관지 천식을 연구하기에는 적당치 못하다고 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제48권4호
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• pp.487-499
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• 2000

연구배경 : 급성호흡곤란증후군은 다양한 원인으로 유발된 폐포와 모세혈관 사이의 투과성 증가로 폐부종이 발생하여 저산소성 호흡부전이 유발되는 증후군으로, 여러 종류의 surfactant의 이상이 관찰되어 외부에서 기관을 통해 surfactant를 공급하는 치료방법이 많이 시도되었다. 본 연구에서는 흰쥐를 대상으로 기판내로 내독소를 주입하여 급성 폐손상을 유발한 다음 기관내로 surfactant를 투여하여 치료효과를 알아보았다. 방 법 : 흰쥐를 각각 5마리씩 네 군으로 나누어 제1군은 기관대로 생리식염수를 30분 간격으로 주입하였고, 제2군은 기관내로 내독소를 주입한 이후 30분 뒤에 기관내로 생리식염수를 주입하였으며, 제3군과 4군은 기관내로 내독소를 주입한 후 각각 30분과 5시간 뒤에 기관내로 surfactant를 주입하였다. 결 과 : 생리식영수만 기관내로 주입한 제1군에 비해서 내독소를 기관내로 주입한 제2군과 3군, 4군에서는 호흡수가 증가하고, 흡기유량이 감소하였으며, 기도저항을 나타내는 지표인 Penh은 제2군에서만 증가되었다. 동맥혈액산소분압은 제 2군에서만 유의하게 감소하였다. 기관내 내독소 투여후 24시간에 얻은 기관지폐포세척액의 단백농도는 제 2군에서만 증가하였다. 기관지폐포세척액내의 세포수는 내독소를 투여받은 제2군과 3군, 4군에서 모두 증가하였고 구성세포는 다형백혈구가 다수를 이루고 있었다. 폐조직검사에서 제2군의 폐포내로 다형백혈구를 위주로하는 염증세포의 침윤과 폐포벽의 비후소견이 관찰되었으며, 제3군 및 제4군에서도 비슷한 염증소견이 관찰되었으나 염증의 정도는 제2군에서 제일 심하였다. 결 론 : 기관내 sufactant 투여는 기관내 내독소 투여로 유발된 흰쥐의 급성폐손상에서 의미있는 치료효과를 나타내었다.

• Clinical and Experimental Pediatrics
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• 제56권11호
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• pp.482-489
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• 2013

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.