• 생명과학회지
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• 제19권12호
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• pp.1777-1786
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• 2009

사이모신 베타 4와 VEGF의 발현을 여러 인간 조직에서 tissue microarray를 사용하여 조사하였다. 사이모신 베타 4는 간, 이자, 침샘의 관상피, 심장에서 강한 발현을 보였으며 피부, 폐, 이자, 림프절, 갑상선, 요관, 폐와 부신의 혈관 내피세포 등에서 중간 수준의 발현 양상을 보였다. VEGF의 발현 양상은 대체적으로 사이모신 베타 4와 동일하였으며 이자, 요관, 유선, 간, 식도, 신장, 폐, 부신 등의 혈관 내피세포에서 강하게 발현되었다. 이러한 결과를 통해 사이모신 베타 4는 간, 이자, 침샘의 관상피, 심장에서 중요한 역할을 담당하며 VEGF와 같은 발현 양상을 보여 혈관 신생작용에 관여함을 확인하였다.

• Biomolecules & Therapeutics
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• 제26권6호
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• pp.553-559
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• 2018

Investigations into the development of new therapeutic agents for lung inflammatory disorders have led to the discovery of plant-based alternatives. The rhizomes of Anemarrhena asphodeloides have a long history of use against lung inflammatory disorders in traditional herbal medicine. However, the therapeutic potential of this plant material in animal models of lung inflammation has yet to be evaluated. In the present study, we prepared the alcoholic extract and derived the saponin-enriched fraction from the rhizomes of A. asphodeloides and isolated timosaponin A-III, a major constituent. Lung inflammation was induced by intranasal administration of lipopolysaccharide (LPS) to mice, representing an animal model of acute lung injury (ALI). The alcoholic extract (50-200 mg/kg) inhibited the development of ALI. Especially, the oral administration of the saponin-enriched fraction (10-50 mg/kg) potently inhibited the lung inflammatory index. It reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Histological changes in alveolar wall thickness and the number of infiltrated cells of the lung tissue also indicated that the saponin-enriched fraction strongly inhibited lung inflammation. Most importantly, the oral administration of timosaponin A-III at 25-50 mg/kg significantly inhibited the inflammatory markers observed in LPS-induced ALI mice. All these findings, for the first time, provide evidence supporting the effectiveness of A. asphodeloides and its major constituent, timosaponin A-III, in alleviating lung inflammation.

• Tuberculosis and Respiratory Diseases
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• 제39권2호
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• pp.120-130
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• 1992

연구배경 : 급성 폐손상의 기전에 관한 연구는 많이 진행되어 있으나 아직 확실한 결론을 내리기에는 미흡한 실정이다. 최근에 산소기의 병인론적 역할에 관한 관심이 고조되고 있으나 이것도 아직 확실히 규명되지 못한 실정이고 내독소에 의한 백서의 급성 폐손상에 관해서는 경험이 일천한 상태이다. 이에 저자들은 백서에서 내독소투여 후 시간경과에 따른 폐포내 호중구 침윤과 폐포-모세혈관 투과성의 변화를 관찰하고 hydroxyl radical 탐식제인 DMTU와 hydroxyl radical 형성에 중요한 역할을 하는 철분제거제인 DFX 전처치가 이에 미치는 영향을 관찰하여 hydroxyl radical이 내독소에 의한 백서의 급성 폐손상에서 호중구의 이동과 폐포-모세혈관 투과성의 증가에 마치는 영향을 평가하고자 본 연구를 시행하였다. 방법 : 50마리의 백서를 대조군 (n=5, 6hrs; n=5, 24hrs), 내독소 투여군 (n=10, 6hrs; n=10 24hrs), DMTU 전처치군 (n=10, 6hrs) 과 DFX 전처치군 (n=10, 6hrs) 으로 나누어 희생하기 30분전에 $^{125}I$을 붙인 bovine serum albwnin을 꼬리 정맥에 주사하였다. 내독소를 투여하고 6시간과 24시간이 경과한 후 백서를 희생시켜서 폐조직과 말초혈액 1 ml의 방사능을 측정하여 이 둘의 비를 폐포-모세혈관 투과성의 지표로 사용하였다. 다른 52마리의 백서를 위와 같이 4개의 군으로 나누어 [대조군 (n=5, 6hrs; n=5, 24hrs), 내독소투여군 (n=7, 6hrs; n=8, 24hrs), DMTU 전처치군 (n=6, 6hrs; n=9, 24hrs)과 DFX 전처치군 (n=5, 6hrs; n=7, 24hrs)] 내독소를 투여하고 6시간과 24시간이 경과한 후 희생시켜 말초혈액과 기관지폐포세척액의 구성세포와 폐의 병리조직학적 소견을 관찰하였다. 결과 : 내독소를 투여하고 6시간이 경과한 후 폐포-모세혈관 투과성이 증가되었다가 24시간이 경과한 후 정상대조군 수준으로 회복되는 양상을 보였는데 6시간만에 DMTU와 DFX 전처치로 유의하게 완화되었다. 폐조직으로의 호중구 침윤은 내독소를 투여하고 24시간이 경과한 후 관찰되었는데 이는 DMTU와 DFX 전처치로 완화되지 않았다. 결론 : 이상의 결과로 내독소에 의한 백서의 급성 폐손상에서 hydroxyl radical은 호중구의 이동에는 관여하지 않을 것으로 생각되며 주로 폐포-모세혈관 투과성 증가에 관여할 것으로 생각된다.

• 생명과학회지
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• 제20권11호
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• pp.1725-1728
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• 2010

미니돼지에서 폐 환기/관류 신티그라피를 실시한 결과 환기스캔에서는 기능적 분포는 왼쪽 폐가 44.2%, 오른쪽 폐에서는 56.2%로 나타났으며, 관류스캔에서는 왼쪽 폐가 46.87%, 오른쪽 폐가 54.97% 임을 확인할 수 있었고 사람의 폐용적과 유사한 결과를 보임을 확인할 수 있었다. 또한 다른 방사성가스보다 짧은 시간을 필요로 하며 기계적 환기로도 스캔이 가능한 Technegas로 환기 스캔을 실시하여 미니돼지의 마취시간을 줄 일 수 있었으며 미니돼지에서 더 용이하게 폐기능을 측정할 수 있었다. 따라서 본 연구를 통해 폐 환기/관류 신티그라피가 미니돼지에서 정상 폐기능 및 폐질환과 관련된 실험을 할 때 폐기능을 측정하는 좋은 진단법이 될 수 있으며 미니돼지의 정상 폐기능에 관한 연구가 앞으로 폐질환과 관련된 미니돼지의 실험에 대한 정보를 제공할 수 있으리라 생각된다.

• Journal of Ginseng Research
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• 제42권4호
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• pp.476-484
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• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

• Tuberculosis and Respiratory Diseases
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• 제83권4호
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• pp.312-320
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• 2020

Background: Systemic sclerosis (SSc) involves multiple organ systems and has the highest mortality among connective tissue diseases. Interstitial lung disease is the most common cause of death among SSc patients and requires closer studies and follow-ups. This study aimed to identify lung function changes and predictors of progressive disease in systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: A retrospective study extracted SSc patients from an electronic database January 2002-July 2019. Eligible cases were SSc patients >age 15 diagnosed with SSc-ILD. Factors associated with progressive disease were analyzed by univariate and multivariate logistic regression analyses. Results: Seventy-eight SSc-ILD cases were enrolled. Sixty-five patients (83.3%) were female, with mean age of 44.7±14.4, and 50 (64.1%) were diffuse type SSc-ILD. Most SSc-ILD patients had crackles (75.6%) and dyspnea on exertion (71.8%), and 19.2% of the SSc-ILD patients had no abnormal respiratory symptoms but had abnormal chest radiographic findings. The most common diagnosis of SSc-ILD patients was non-specific interstitial pneumonia (43.6%). The lung function values of diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume declined in progressive SSc-ILD during a 12-month follow-up. Male and no previous aspirin treatment were the two significant predictive factors of progressive SSc-ILD with adjusted odds ratios of 5.72 and 4.99, respectively. Conclusion: This present study showed that short-term lung function had declined during the 12-month follow-up in progressive SSc-ILD. The predictive factors in progressive SSc-ILD were male sex and no previous aspirin treatment. Close follow-up of the pulmonary function tests is necessary for early detection of progressive disease.

• 한국임상수의학회지
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• 제32권4호
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• pp.313-318
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• 2015

The lung opacity on radiography is influenced by various factors. The physical density of the lung and the attenuation ensured on computed tomography (CT) scans is determined by three components : lung tissue, blood, and air. Temporary right lateral recumbency may responsible for the increase of opacity on ventrodorsal projection view. Thus, our aim is to demonstrate that the effect of right lateral recumbency posture on right lung opacity using radiograph and CT scan. In this study, 62 dogs without clinical or radiologic signs of cardiopulmonary disease are selected. Thorax radiographs per 30 seconds for 2 minutes (30s, 60s, 90s, 120s) were performed for 62 dogs. After discussion of the radiographic findings of lung field by two radiologists and a student at Chungbuk national university veterinary medical center a consensus opinion was recorded. Computed tomography per a minute (1 min, 2 min) for 2 minutes were performed for 2 dogs. Mean x-ray attenuation of lung was measured quantitatively using software at two levels (aortic arch and basal level). Among 62 dogs with radiograph comparison, 9.3% of dogs showed influence by postural effect. However, all 2 dogs with computed tomography comparison, showed influence by postural effect. In conclusion, position dependent changes of lung density in CT exam are not consistent with thoracic radiograph.

• 한국동물위생학회지
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• 제41권4호
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• pp.263-269
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• 2018

Developing drugs targeting respiratory pathogen is essential to control respiratory diseases. Many experiments have been performed under in vivo situation. However, in vivo experiments have economical and ethical issues. The objective of this study was to determine the possibility of developing an ex vivo lung culture system with possible application for respiratory infection studies. After isolating lungs from naïve pigs, agarose-inflated lung tissues were prepared and sliced manually. These sliced lung tissues were then subsequently placed on 24-well plates. Eight different combinations of media were used to determine the optimum ex vivo lung culture condition. In addition, lung tissues were infected with porcine reproductive and respiratory syndrome (PRRS) virus at a titer of $1{\times}10^4\;TCID_{50}/mL$. Virus growth was confirmed by titration in MARC-145 cells at 2, 4, 6 days post infection (dpi). We found that ex vivo lung culture in physiological environment was not media specific based on histopathology and cytotoxicity. However, under virus-infected condition, thickened alveolar walls in the lung tissues and stable virus titers at 2, 4, 6 dpi were shown in F12K medium suggesting that it was useful for tissue maintenance and virus infection using PRRS virus infected lung tissues. The present study shows the possibility of using porcine ex vivo lung model for respiratory infection studies.

• 대한이식학회지
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• 제28권3호
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• pp.154-159
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• 2014

Background: Lung transplantation (LTx) is a life-saving treatment for patients with end-stage lung disease; however, the shortage of donor lungs has been a major limiting factor to increasing the number of LTx. Growing experience following LTx using donor lungs after cardiac death (DCD) has been promising, although concerns remain. The purpose of this study was to develop a DCD lung harvest model using an ex vivo lung perfusion (EVLP) system and to assess the function of presumably damaged lungs harvested from the DCD donor in pigs. Methods: The 40 kg pigs were randomly divided into the control group with no ischemic lung injury (n=5) and the study group (n=5), which had 1 hour of warm ischemic lung injury after cardiac arrest. Harvested lungs were placed in the EVLP circuit and oxygen capacities (OC), pulmonary vascular resistance (PVR), and peak airway pressure (PAP) were evaluated every hour for 4 hours. At the end of EVLP, specimens were excised for pathologic review and wet/dry ratio. Results: No statistically significant difference in OC (P=0.353), PVR (P=0.951), and PAP (P=0.651) was observed in both groups. Lung injury severity score (control group vs. study group: 0.700±0.303 vs. 0.870±0.130; P=0.230) and wet/dry ratio (control group vs. study group: 5.89±0.97 vs. 6.20±0.57; P=0.560) also showed no statistically significant difference between the groups. Conclusions: The function of DCD lungs assessed using EVLP showed no difference from that of control lungs without ischemic injury; therefore, utilization of DCD lungs can be a new option to decrease the number of deaths on the waiting list.

• IMMUNE NETWORK
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• 제23권6호
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.