http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할
김제형 ( Je Hyeong Kim ),윤대위 ( Dae Wui Yoon ),허규영 ( Gyu Young Hur ),정기환 ( Ki Hwan Jung ),이승룡 ( Sung Yong Lee ),이상엽 ( Sang Yeub Lee ),신철 ( Chol Shin ),심재정 ( Jae Jeong Shim ),인광호 ( Kwang Ho In ),유세화 ( Se H 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.4
연구배경: 활성산소종은 기계환기로 인한 폐손상 (ventilator-induced lung injury, VILI)에서 주요한 역할을 한다. Poly (ADP-ribose) polymerase-1 (PARP1)은 DNA 손상 감시 기능을 하는 단백질로서, DNA 파열을 신호하고 복구에 관여한다. 그러나 활성 산소종에 의한 것과 같은 심한 유전자 손상을 받게 되면, 과활성화되어-nicotinamide adenine dinucleotide (NAD(+))의 결핍을 통한 세포의 사멸을 초래하여, 염증 반응을 일으킨다. 본 연구에서는 VILI의 기전에 있어서 PARP1의 역할 및 그 억제제의 효과를 고찰하고자 하였다. 방법: 48마리의 수컷 C57BL/6 생쥐를 겉보기 수술군 (Sham군), 폐보호적 환기군(lung protective ventilation group, LPV군), 기계환기기로 인한 폐손상군 (ventilator-induced lung injury group, VILI군) 및 PARP1 억제제인 PJ34 전처치 후 기계환기로 인한 폐손상군 (PJ34+VILI군)으로 나누어 실험하였다. LPV군에 대한 기계환기는 PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min. 조건으로, VILI 및 PJ34+VILI군에 대해서는 PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min.의 조건으로 2시간 동안 시행하였다. PJ34+VILI군에서 PARP1 억제제로는, PJ34 20 mg/Kg을 기계환기 2시간 전에 복강 내로 주사하였다. VILI의 정도는 습건중량비 및 급성폐손상 지수로 측정하였고, PARP1의 활성은 biotinylated NAD를 이용한 면역조직화학적 방법을 이용하였다. 또한 기관지폐포세척액 (bronchoalveolar lavage fluid, BALF) 내에서 myeloperoxidase (MPO) 활성 및 tumor necrosis factor- (TNF- ), interleukin-1 (IL-1), IL-6 등의 염증성 시토카인의 농도를 측정하였다. 결과: PJ34+VILI군에서 VILI군과 비교하여, PJ34 전처치로 인하여 폐손상의 정도가 현저히 감소 하였다(p<0.05). 5개의 고배율 시야에서 관찰한 PARP1의 활성을 보이는 세포의 수는 VILI군에서 유의하게 증가하였고, PJ34+VILI군에서 현저히 감소하였다(p=0.001). BALF 내에서 측정한 MPO 활성 및 TNF-, IL-1, IL-6의 농도 역시 PJ34+VILI군에서 의미 있게 감소하였다(p<0.05). 결론: VILI의 기전에 있어서 PARP1의 과활성이 주요한 역할을 하고, PARP1 억제제가 MPO 활성 및 염증성 시토카인의 감소와 함께 VILI의 발생을 억제한다. Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through-nicotinamide adenine dinucleotide (NAD(+)) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min+2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min+2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, TNF-, IL-1, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines. (Tuberc Respir Dis 2006; 60: 451-463)
기계환기로 인한 백서의 급성 폐손상에서 Matrix Metalloproteinase Inhibitor의 효과
김제형 ( Kim Je Hyeong ),박수연 ( Park Su Yeon ),허규영 ( Heo Gyu Yeong ),이승헌 ( Lee Seung Heon ),이상엽 ( Lee Sang Yeob ),박상면 ( Park Sang Myeon ),서인범 ( Seo In Beom ),신철 ( Sin Cheol ),심재정 ( Sim Jae Jeong ),인광호 ( I 대한결핵 및 호흡기학회 2002 Tuberculosis and Respiratory Diseases Vol.53 No.6
Ovalbumin으로 감작된 기니픽에서 Allergen 흡입으로 인한 즉시형 기관지 수축반응에 대한 비침습적 측정
김제형 ( Je Hyeong Kim ),심재정 ( Jae Jeong Shim ),이승룡 ( Sung Yong Lee ),권영환 ( Young Hwan Kwon ),이소라 ( So Ra Lee ),이상엽 ( Sang Youb Lee ),조재연 ( Jae Youn Cho ),인광호 ( Kwang Ho In ),유세화 ( Se Hwa Yoo ),강경호 ( Kyu 대한결핵 및 호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.1
리포다당질로 유도된 급성 폐손상 후 섬유화증식에서 Transglutaminase-2의 역할
김제형 ( Je Hyeong Kim ) 대한결핵 및 호흡기학회 2010 Tuberculosis and Respiratory Diseases Vol.69 No.5
Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which 50 μL of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/50 μL of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor (NF)-κB were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-β1 were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory`s phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-α and IL-1β concentrations and NF-κB activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-β1 concentration, and Mallory`s PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.
리포다당질로 인한 직접성 급성폐손상에서 Nuclear Factor-κB Decoy Oligodeoxynucleotide의 효과
김제형 ( Je Hyeong Kim ),윤대위 ( Dae Wui Yoon ),정기환 ( Ki Hwan Jung ),김혜옥 ( Hye Ok Kim ),하은실 ( Eun Sil Ha ),이경주 ( Kyoung Ju Lee ),허규영 ( Gyu Young Hur ),이승룡 ( Sung Yong Lee ),이상엽 ( Sang Yeub Lee ),신철 ( Chol 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.67 No.2
Background: The pathophysiologic mechanisms of early acute lung injury (ALI) differ according to the type of primary insult. It is important to differentiate between direct and indirect pathophysiologic pathways, and this may influence the approach to treatment strategies. NF-κB decoy oligodeoxynucleotide (ODN) is a useful tool for the blockade of the expression of NF-κB-dependent proinflammatory mediators and has been reported to be effective in indirect ALI. The purpose of this study was to investigate the effect of NF-κB decoy ODN in the lipopolysaccharide (LPS)-induced direct ALI model. Methods: Five-week-old specific pathogen-free male BALB/c mice were used for the experiment. In the preliminary studies, tumor necrosis factor (TNF)-α, interleukine (IL)-6 and NF-κB activity peaked at 6 hours after LPS administration. Myeloperoxidase (MPO) activity and ALI score were highest at 36 and 48 hours, respectively. Therefore, it was decided to measure each parameter at the time of its highest level. The study mice were randomly divided into three experimental groups: (1) control group which was administered 50 μL of saline and treated with intratracheal administration of 200 μL DW containing only hemagglutinating virus of Japan (HVJ) vector (n=24); (2) LPS group in which LPS-induced ALI mice were treated with intratracheal administration of 200 μL DW containing only HVJ vector (n=24); (3) LPS+ODN group in which LPS-induced ALI mice were treated with intratracheal administration of 200 μL DW containing 160 μg of NF-κB decoy ODN and HVJ vector (n=24). Each group was subdivided into four experimental subgroups: (1) tissue subgroup for histopathological examination for ALI at 48 hours (n=6); (2) 6-hour bronchoalveolar lavage (BAL) subgroup for measurement of TNF-α and IL-6 in BAL fluid (BALF) (n=6); (3) 36-hour BAL subgroup for MPO activity assays in BALF (n=6); and (4) tissue homogenate subgroup for measurement of NF-κB activity in lung tissue homogenates at 6 hours (n=6). Results: NF-κB decoy ODN treatment significantly decreased NF-κB activity in lung tissues. However, it failed to improve the parameters of LPS-induced direct ALI, including the concentrations of tumor necrosis factor-α and interleukin-6 in BALF, myeloperoxidase activity in BALF and histopathologic changes measured by the ALI score. Conclusion: NF-κB decoy ODN, which has been proven to be effective in indirect models, had no effect in the direct ALI model.
결핵성 흉막염 환자에서 NRAMP1 유전자 다형성에 대한 연구
김제형 ( Je Hyeong Kim ),김병규 ( Byung Gyu Kim ),정기환 ( Ki Hwan Jung ),이상엽 ( Sang Myun Park ),박상면 ( Sang Youb Lee ),이신형 ( Sin Hyung Lee ),신철 ( Cheol Sin ),조재연 ( Jae Youn Cho ),심재정 ( Jae Jeong Shim ),인광호 ( K 대한결핵 및 호흡기학회 2000 Tuberculosis and Respiratory Diseases Vol.48 No.2
김제형 ( Je Hyeong Kim ) 대한내과학회 2014 대한내과학회지 Vol.86 No.5
Ventilator-induced lung injury (VILI) is the additional inflammatory damage caused by mechanical ventilation, especially in acute respiratory distress syndrome (ARDS). VILI can induce a systematic inflammatory response, resulting in multiple organ dysfunction syndrome, which is the major cause of death in ARDS patients. The two main mechanisms of VILI are physical stretch injury caused by a high tidal volume and shearing force caused by the reopening and collapse of alveoli in atelectatic lung. Protective ventilation strategies to prevent VILI include low tidal volume ventilation, high positive end-expiratory pressure, prone position ventilation, the alveolar recruitment maneuver, and extracorporeal membrane oxygenation. The clinical support is strongest for low tidal volume ventilation, which should be used in all cases of ARDS. However, its effectiveness might be limited because of the severe spatial heterogeneity of the lung involvement, which cannot completely prevent regional alveolar distension. Although there is insufficient clinical evidence supporting the other strategies, and they are controversial, various strategies other than low tidal volume ventilation should be considered in selected clinical conditions in which they might be effective. (Korean J Med 2014;86:529-536)
안지오텐신 전환효소 억제제에 의한 건성 기침의 발생과 안지오텐신 전환효소 유전자 다형성과의 관계
김제형 ( Je Hyeong Kim ),정혜철 ( Hye Cheol Jeong ),김경규 ( Kyung Kyu Kim ),이승룡 ( Sung Yong Lee ),권영환 ( Young Hwan Kwon ),이소라 ( So Ra Lee ),이상엽 ( Sang Youb Lee ),이신형 ( Sin Hyung Lee ),차대룡 ( Dae Ryong Cha ),조재 대한결핵 및 호흡기학회 1999 Tuberculosis and Respiratory Diseases Vol.46 No.2
백서 천식에서 면역 증강성 CpG 올리고 뉴클레오티드 투여의 효과
이신형 ( Lee Sin Hyeong ),김제형 ( Kim Je Hyeong ),정혜철 ( Jeong Hye Cheol ),김경규 ( Kim Gyeong Gyu ),정기환 ( Jeong Gi Hwan ),김병규 ( Kim Byeong Gyu ),이승헌 ( Lee Seung Heon ),박상면 ( Park Sang Myeon ),신철 ( Sin Cheol ) 대한결핵 및 호흡기학회 2001 Tuberculosis and Respiratory Diseases Vol.50 No.1