• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1343-1352
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• 1997

연구배경 : 패혈증이나 이에 합병된 급성호흡곤란증후군 환자들은 고열을 동반하는 경우가 많다. 발열은 조직의 대사를 항진시키므로 조직내 산소공급에 제한이 초래되는 패혈증 환자들에서 발열이 동반되는 경우 열을 동반하지 않는 경우보다 중요기관의 산소공급이 상대적으로 저하될 가능성이 있다. 반면, 발열상태는 조직내 열충격단백질 (heat shock protein, HSP)의 생성을 유도하여 패혈증에 의한 비가역적인 손상으로부터 세포들을 보호함으로써 생체의 방어기전에 유려하게 작용할 수도 있어 패혈중 이에 합병된 급성 폐손상 환자들의 발열에 대한 임상적 의미는 아직 규명되어 있지않았다. 본 연구는 열을 전처치 하였거나 하지 않은 Sprague-Dawley rat의 기도에 TNF를 주입한 후 TNF에 의해 유도되는 급성 폐손상의 정도를 비교함으로써 열이 급성 폐손상에 미치는 효과를 관찰하고자 하였다. 대상 및 방법 : 급성 폐손상의 지표로는 백서의 우측폐내 $I^{125}$의 분당 측정량 대비 1mL의 혈중내 $I^{125}$의 분당 측정량의 비율로 정의한 단백누출지표와 백혈구의 조직내 침윤정도를 반영하는 myeloperoxidase(MPO)의 활성도를 측정하였다. 결과는 평균(${\pm}$ 표준오차)로 표기하였다. 결 과 : 백서의 기도에 생리식염수를 주입한 백서들은 열을 전처치 하였거나 하지 않은 경우 두 군사이의 단백 누출 지표는 각각 0.099(${\pm}0.024$) 및 0.123(${\pm}0.005$)로서 차이가 없었으며 MPO도 4.58(${\pm}0.79\;U/gm$) 및 7.32(${\pm}0.97\;U/gm$)로서 열을 전처치 할 경우 다소 감소되는 경향(P=0.064)를 보였으나 차이가 없었다. 백서의 기도에 TNF-$\alpha$을 주입한 치료군에서 열 전처치한 백서군은 단백누출지표 0.137(${\pm}0.012$) 및 MPO 7.01(${\pm}0.89\;U/gm$)로서 열 전처치 않은 백서군 단백누출지표 0.186(${\pm}0.015$) 및 MPO 14.11(${\pm}1.08\;U/gm$)에 비해 낮았으며(각 P<0.05) 정상군과는 차이가 없었다. MPO 활성도가 단백 증가되었다(r=0.564, P<0.005). 열 전처치 하지 않은 백서에 비해 열 전처치한 백서의 폐 조직내 HSP 72 단백질의 발현은 열 충격 후 18시간 및 23시간 뒤에도 증가되어 나타났다. 결 론 : 백서에 열을 전처치 할 경우 TNF-$\alpha$로 유도되는 급성 폐손상이 경감되므로 발열이 백서의 방어기전에 유리하게 작용한 것으로 사료되었다.

• 대한본초학회지
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• 제29권6호
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• pp.15-20
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• 2014

Objectives : Commiphora myrrha (CM) has been used in traditional medicine for treating disease such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, the protective effects of CM on acute pancreatitis (AP) has not been reported. Thus, the aim of this study was to evaluate the protective effects of CM water extract on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) every hour for 6 times. Water extract of CM (0.1, 0.2, or 0.5 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas was rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of CM significantly inhibited pancreatic weight/body weight ratio, pancreas histological injury. And CM administration inhibited the serum digestive enzyme elevation such as amylase and lipase on cerulein-induced pancreatitis. In addition, Pancreas MPO activity which indicates neutrophil infiltration was inhibited by CM extract on cerulein-induced pancreatitis. Conclusions : In conclusion, our results could suggest that pre-treatment of CM reduces the severity of cerulein-induced AP. Therefore, CM could be used as a protective agent against AP. Also, this study could give a clinical basis that CM could be a drug or agent to prevent AP.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.37-44
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• 1998

This study was performed to examine the effects of DA-9601, a novel antiulcer agent extracted from Artemisiae Herba, on radiation colitis in the rat. Female Wistar rats received a 30 Gy dose of irradiation to the 2 cm of distal colon in length using an intrarectal applicator system. 30 mg/tg or 100 mg/kg of DA- 9601 was administered orally 30 min before and 4 h after radiation on day 1. And the same dose of DA-9601 was given to the animals twice a day from day 2 to 14. As a reference control, sucralfate suspension (100 or 300 mg/head) was given as an enema based on the same treatment schedule of DA-9601. Body weight change and the frequency of diarrhea were recorded during the observation period as markers of radiationinduced injury, All animals were sacrificed on day 15 for evaluation of macro- and microscopic findings and mucosal myeloperoxidase (MPO) activity. Radiated animals showed diarrhea, mucosal redness and histologic changes characterized by edema and eosinophilic infiltration of the periglandular lamina propria with loss of colonic epithelium. Radiation also significantly increased mucosal MfO activity of affected colon f\\\\\\\\`<0.05). However, most of these changes were completely protected by oral administration with DA-9601. DA-9601 reduced radiation-induced histologic alteration significantly in a dose-related manner (P<0.05). In addition, mucosal MPO activity in rats receiving high dose of DA-9601 decreased significantly when compared with that in radiated control. High dose of sucralfate (300 mg/head) alleviated radiation-induced histologic lesion, but failed to reach statistical significance. The results of this study suggest that DA-9601 can be useful for the prevention of acute clinical symptoms of radiation proctocolitis and that decrease of mucosal MPO by DA-9601 plays a role in its protective mechanism(s), at least in part.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.405-414
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• 1999

The role of platelet-activating factor (PAF) was investigated in intestinal ischemia/reperfusion (I/R) induced acute lung injury associated with oxidative stress. To induce acute lung injury following intestinal I/R, superior mesenteric arteries were clamped with bulldog clamp for 60 min prior to the 120 min reperfusion in Sprague-Dawley rats. Acute lung injury by intestinal I/R was confirmed by the measurement of lung leak index and protein content in bronchoalveolar lavage (BAL) fluid. Lung leak and protein content in BAL fluid were increased after intestinal I/R, but decreased by WEB 2086, the PAF receptor antagonist. Furthermore, the pulmonary accumulation of neutrophils was evaluated by the measurement of lung myeloperoxidase (MPO) activity and the number of neutrophils in the BAL fluid. Lung MPO activity and the number of neutrophils were increased (p＜0.001) by intestinal I/R and decreased by WEB 2086 significantly. To confirm the oxidative stress induced by neutrophilic respiratory burst, gamma glutamyl transferase (GGT) activity was measured. Lung GGT activity was significantly elevated after intestinal I/R (p<0.001) but decreased to the control level by WEB 2086. On the basis of these experimental results, phospholipase $A_2\;(PLA_2),$ lysoPAF acetyltransferase activity and PAF contents were measured to verify whether PAF is the causative humoral factor to cause neutrophilic chemotaxis and oxidative stress in the lung following intestinal I/R. Intestinal I/R greatly elevated $PLA_2$ activity in the lung as well as intestine (p<0.001), whereas WEB 2086 decreased $PLA_2$ activity significantly (p<0.001) in both organs. LysoPAF acetyltransferase activity, the PAF remodelling enzyme, in the lung and intestine was increased significantly (p<0.05) also by intestinal I/R. Accordingly, the productions of PAF in the lung and intestine were increased (p<0.001) after intestinal I/R compared with sham rats. The level of PAF in plasma was also increased (p<0.05) following intestinal I/R. In cytochemical electron microscopy, the generation of hydrogen peroxide was increased after intestinal I/R in the lung and intestine, but decreased by treatment of WEB 2086 in the lung as well as intestine. Collectively, these experimental results indicate that PAF is the humoral mediator to cause acute inflammatory lung injury induced by intestinal I/R.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.469-477
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• 2013

This study investigated effect of extract containing quercetin-3-O-${\beta}$-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.219-226
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• 2000

In order to elucidate the role of platelet activating factor (PAF) in the acute lung injury induced by endotoxin (ETX), activities of phospholipase A2, lyso PAF acetyltransferase and oxidative stress by neutrophilic respiratory burst were probed in the present study. To induce acute lung injury, $100\;{\mu}g$ of E.coli ETX (type 0127; B8) was instilled directly into the tracheae of Sprague-Dawley rats. Five hours after the ETX instillation, induction of acute lung injury was confirmed by lung leak index and protein contents in the bronchoalveolar lavage (BAL) fluid. At the same time, lung phospholipase A2 (PLA2) activity and expression of group I and II secretory type PLA2 were examined. In these acutely injured rats, ketotifen fumarate, known as lyso PAF acetyltransferase inhibitor and mepacrine were administered to examine the role of PAF in the pathogenesis of the acute lung injury. To know the effect of the ETX in the synthesis of the PAF in the lungs, lyso PAF acetyltransferase activity and PAF content in the lungs were measured after treatments of ETX, ketotifen fumarate and mepacrine. In addition, the role of neutrophils causing the oxidative stress after ETX was examined by measuring lung myeloperoxidase (MPO) and enumerating neutrophils in the BAL fluid. To confirm the oxidative stress in the lungs, pulmonary contents of malondialdehyde (MDA) were measured. After instillation of the ETX in the lungs, lung leak index increased dramatically (p＜0.001), whereas mepacrine and ketotifen decreased the lung leak index significantly (p＜0.001). Lung PLA2 activity also increased (p＜0.001) after ETX treatment compared with control, which was reversed by mepacrine and ketotifen (p＜0.001). In the examination of expression of group I and II secretory PLA2, mRNA synthesis of the group II PLA2 was enhanced by ETX treatment, whereas ketotifen and WEB 2086, the PAF receptor antagonist, decreased the expression. The activity of the lysoPAF acetyltransferase increased (p＜0.001) after treatment of ETX, which implies the increased synthesis of PAF by the remodelling of lysoPAF in the lungs. Consequently, the contents of the PAF in the lungs were increased by ETX compared with control (p＜0.001), while mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the synthesis of the PAF in the lungs of ETX treated rats. The infiltration of the neutrophils was confirmed by measuring and enumerating lung MPO and the neutrophils in the BAL fluid respectively. Compared with control, ETX increased lung MPO and number of neutrophils in BAL significantly (p＜0.001) whereas mepacrine and ketotifen decrerased number of neutrophils (p＜0.001) and MPO (p＜0.05, p＜0.001, respectively). The lung MDA contents were also increased (p＜0.001) by ETX treatment, but treatment with mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the lung MDA contents. Collectively, we conclude that ETX increases PLA2 activity, and that the subsequently increased production of PAF was ensued by the remodelling of the lyso PAF resulting in tissue injury by means of oxidative stress in the lungs.

• 한국임상수의학회지
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• 제26권1호
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• pp.8-16
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• 2009

항암제에 의해 흰쥐에서 다형핵 백혈구(polymorphonuclear leukocytes, PMN) 의 활성산소종(reactive oxygen species, ROS)과 산화질소(nitric oxide, NO)의 생성변화에 대해 연구하였다. 최근 자극유도인자에 의한 PMN의 호흡방출은 protein kinase C (PKC)의 활성, inositol phosphate transduction pathway의 활성, 그리고 intracellular [$Ca^{2+}$]와 관계가 있다고 밝혀졌으며, 본 연구에서 사용된 항암제(cyclophosphamide, cisplatin, tamoxifen, doxifluridine)중 일부는 화학치료제로써 비특이적으로 면역을 억제하는데 사용되고 있다. 암 치료 시 백혈구의 방어기능에 미치는 영향을 연구하기 위한 목적으로 in vitro에서 각 항암제를 처리한 PMN을 배양하여 ROS와 NO의 생성변화와 이차적 신호전달계인 phospholipase C(PLC), D(PLD), PKC, tyrosine phosphorylation kinase (TPK)와 phosphatidylinositol-3 kinase의 억제율을 측정하였다. PMN에 각각cyclophosphamide, cisplatin, tamoxifen, doxifluridine을 short term(${\leq}4hrs$) 처리시, formylmethionyl-leucy1-phenylalanine (FMLP) 자극에 의해 호흡방출의 증가가 나타났다. 반면, long term (8hrs) 처리 시, ROS의 생성은concentration-dependent 방법으로 감소되었다.

• 한방재활의학과학회지
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• 제30권3호
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• pp.57-69
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• 2020

Objectives The aim of this study was to investigate the inhibitory effect of ChondroT in indomethacin-induced gastric mucosal injury rat model. Methods Sprague-Dawley rats were randomly assigned to intact, control Joins, Celebrex, ChondroT50 and ChondroT200. Indomethacin (25 mg/kg) was used to induce damage to the gastric mucosal injury. ChondroT was administered by orally to inhibit the indomethacin-induced gastric mucosal injury. At the end of the experiment, pH level in stomach, stomach contents volume, tumor necrosis factor-α (TNF-α) level, interleukin-1β (IL-1β) level, prostaglandin E2 (PGE2) level, myeloperoxidase (MPO) activity, erythrocytes, and thrombocytes were measured. Ophthalmologic and histopathological examination was also analyzed. Results pH level in stomach and Stomach contents volume had no difference between Control, PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group. TNF-α level was decreased in PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group and there were no significant difference. IL-1β level was decreased in PC-Joins group and ChondroT200 group compared to control group. PGE2 level had no significant difference between Control, PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group. MPO level and complete blood count level were decreased in PC-Joins, PC-Cele, ChondroT50 and ChondroT200. Symptom score of ophthalmologic examination was decreased in ChondroT50 and ChondroT200 group compared to control group. Conclusion Based on these results, It could be suggested that ChondroT was effective in reducing damage to the gastric mucosal injury. And further study is needed to conduct a rigorous clinical research.

• 대한위암학회:학술대회논문집
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• 대한위암학회 2002년도 제13회 춘계학술대회
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• pp.9-17
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• 2002

위의 parietal cell 혹은 대식세포와 유사한 세포 내부에서 H. pylori가 발견된다는 보고가 있기는 하나 일반적으로 H. pylori는 Shigella와 같은 침습성 세균은 아닌 것으로 알려져 있다. 그럼에도 불구하고 H. pylori에 감염된 위점막에는 많은 수의 호중구를 위시한 염증세포의 침윤이 관찰되는데 H. pylori가 위상피세포에 부착 할 경우 위상피세포를 자극하여 interleukin-8을 위시한 cytokine 을 발현케하고 이에 의하여 호중구 등의 염증세포가 몰려들게 된다. 한편 고유층에 몰려든 호중구에서는 다시 interleukin-8을 위시한 일련의 호중구 활성화 chemokine을 분비하여 염증반응을 증폭해 나갈 것이다. 호중구에서 발현되는 myeloperoxidase나 활성 산소 등도 위점막의 조직 손상에 기여할 것이다. 위상피세포를 덮고 있는 점액층은 위상피세포를 보호한다고 알려져 있으나 H. pylori 감염의 경우 점액층에 의하여 H. pylori의 운동성이 증가하고 이것이 위상피세포로부터의 cytokine 발현을 자극하여 염증반응을 증폭하는데 관여할 가능성도 있다. H. pylori는 위상피세포에 대하여 apoptosis를 유도함과 동시에 고유층에 몰려든 호중구에 대하여는 apoptosis를 억제케하여 궁극적으로 염증반응을 증폭 및 지속시켜 나가는 쪽으로 작용한다. 한편 H. pylori는 위상피세포로부터 COX-2의 발현을 증가시키는데 이는 위상피세포의 apoptosis를 억제하는 방향으로 작용한다. 이외에 H. pylori의 urease에 의하여 발생한 암모니아나 H. pylori 자신이 분비하는 세포독소가 세포 손상을 유발할 가능성도 있다. 상술한 여러 독성 인자들 중 어느 하나가 단독으로 작용하기보다는 여러 인자가 같이 동시에 또는 시차를 두고 작용할 가능성이 많다고 생각된다.(\gamma-FeOOH)$, 침철광$(\alpha-FeOOH)$, 적금광$(\beta-FeOOH)$, 그리고 자철광$(Fe_3O_4)$이다. 인위적 부식에서는 전부 인철광의 부식물이 생성되었고 자연적 부식에서는 모두 침철광의 부식물이 생성되었다. 특히 철제 표면에 자연적으로 생성된 공식 녹을 XRD 분석한 결과 적금광으로 동정되었다. 이런 모든 시편들을 각 탈염방법에 따라 탈염처리한 후 XRD와 SEM-EDS으로 분석한 결과 인철광과 침철광은 어떠한 변화도 보이지 않았고, 다만 적금광으로 동정된 시편만이 잔존하지 않았다. 철기 제작별 $Cl^-$ 이온 추출량과 탈염효과에 대한 비교 실험은 이온 크로마토그래피 분석 결과와 마찬가지로 단조 철제유물이 주조 철제보다 $Cl^-$ 이온을 많이 가지고 있었으며, 탈염 처리 후에는 $Cl^-$ 이온은 전혀 발견되지 않았다. 이상의 결과 $K_2CO_3$와 Sodium 용액은 탈염처리에서 가장 적합한 탈염처리 용액으로 알수가 있었으며 특히 어떠한 탈염 용액으로 유물을 처리한다 해도 철제유물에 생성된 부식물은 제거되지 않는다는 것을 알게 되었다. 따라서 보존처리자는 유물 표면의 부식 상태만을 보고 처리하기 보다는 철기제작물로 고려하여 처리하는 것이 필요하다. 또한 금속에 부식을 야기시키는 $Cl^-$ 이온과 부식물을 완전하게 제거하여 탈염처리를 하는 것이 유물 부식을 최대한 지연시킬 수 있는 것이라 생각된다.TEX>$88\%$)였다.(P=0.063). 결론: 본 연구에서는 MTHFR C/T & T/T 유전자 다형성이 위암의 발생과 그 위치에 대해 관련이 있는 것으로 여겨지고, 흡연력, 음주력과는 관련이 없는 것으로 여겨진다.험이

• Tuberculosis and Respiratory Diseases
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• 제60권4호
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• pp.437-450
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• 2006

연구배경 : 급성호흡곤란증후군의 병인론 중 산화성 스트레스는 페 모세혈관손상의 중요한 기전의 일부이다. 본 연구에서는 호중구에 의한 유리 산소기의 형성이 $PLA_2$의 활성화와 관계가 있음을 근거로 하여 calcium channel blocker인 diltiazem이 내독소에 의한 급성 폐손상에 미치는 영향을 알아보고자 하였다. 방법 : 체중 300 gm 내외의 수컷 Sprague-Dawley흰쥐에서 내독소를 이용하여 급성 폐손상을 유도하고 동시에 내독소 투여 60분전에 diltiazem (3 mg/kg)을 복강 내로 투여하였다. 급성 폐손상이 유도된 흰쥐에서 폐장의 $PLA_2$, 사람에게서 분리된 호중구에서의 $PLA_2$, 폐장의 MPO의 활성도, 폐세척액내의 호중구의 수, surfactant, 단백함량, 호중구에서의 유리 산소기의 생성 등을 측정하였다. 또한 광학 현미경 및 전자 현미경을 이용하여 형태학적인 변화를 관찰하였고, 동시에 전자현미경 세포화학법을 이용하여 폐장내의 유리 산소기의 생성도 검사 하였다. 결과 : 내독소 투여 후 5 시간 후에는 급성 폐손상이 유발되고 폐장 및 호중구의 $PLA_2$, MPO, 폐세척액내의 호중구수, 단백함량 및 surfactant의 함량이 높게 측정되었다. 형태학적으로는 내독소에 의한 급성 페손상이 확인되었고 전자현미경을 이용한 세포화학적 검사에서는 폐장 내 유리 산소기의 생성이 증가되었음을 확인하였다. Diltiazem은 이러한 모든 변화를 감소시키고, 호중구에서의 산소기의 생성도 감소시켜 내독소에 의한 급성 폐손상을 감소 시켰다. 결론 : Diltiazem을 이용한 $PLA_2$의 억제는 내독소에 의한 급성 페손상에서 호중구에 의한 산화성 스트레스를 경감함으로써 그 손상을 줄일 것으로 사료된다.