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Naringin에 의한 천식치료 효과연구

Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene

  • 이창민 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 장정현 (대구한의대학교 임상병리학과) ;
  • 정인덕 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 정영일 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 노경태 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 박희주 (부산대학교 소아과학교실) ;
  • 김종석 (전북대학교 생화학교실) ;
  • 신용규 (중앙대학교 해부학교실) ;
  • 박성남 (부산대학교 의학전문대학원 미생물학 및 면역학교실) ;
  • 박영민 (부산대학교 의학전문대학원 미생물학 및 면역학교실)
  • Lee, Chang-Min (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine) ;
  • Chang, Jeong-Hyun (Department of clinical laboratory Science, College of Health & Therapy, Daegu Haany University) ;
  • Jung, In-Duk (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine) ;
  • Jeong, Young-Il (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine) ;
  • Tae, Noh-Kyung (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine) ;
  • Park, Hee-Ju (Department of Pediatrics, Pusan National University School of Medicine) ;
  • Kim, Jong-Suk (Department of Biochemistry, Chonbuk National University Medical School) ;
  • Shin, Yong-Kyoo (Department of Pharmacology, Chungang University College of Medicine) ;
  • Park, Sung-Nam (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine) ;
  • Park, Yeong-Min (Department of Microbiology and Immunology & National Research Laboratory of Dendritic Cell Differentiation & Regulation, and Medical Research Institute, Pusan National University School of Medicine)
  • 발행 : 2009.06.30

초록

Naringill은 레몬, 오렌지에서 발견되는 flavonoid계열에 속하는 물질로 여러 식물과 과일에 다량 함유되어 있다. 항암, 항산화 작용을 하는 것으로 알려져 있는 Naringin을 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델을 이용하여 치료효과를 알아 보았다. 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포 (Th2 cell)가 생산하는 Il-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 또한, 최근에 Th1/Th2 전사인자로서 GATA-3가 밝혀졌는데 이번 실험에서 Naringin이 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1, Th2 싸이토가인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토가인 (IL-4, 1L-5)의 증가가 관찰되었다. 그러나 Naringin 을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 Naringin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 Naringin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다.

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

키워드

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