• 한국임상수의학회지
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• 제19권3호
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• pp.299-302
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• 2002

Selectin은 조직 염증반응의 초기화에 관여하는 결합 단백질이며, 맥관내피에서 백혈구의 rolling과 tethering을 매개한다. 따라서 selectin inhibitor를 이용하여, 이들 selectin의 수용체인 sLex 에 대한 block을 유도함으로서 염증반응의 초기화를 억제할 수 있다는 가정하에, 본 연구에서는 장기이식 후 reperfusion에서 발생하는 손상에 대한 selectin inhibitor의 효과를 알아보았다. Beagle 견을 사용하여 신장이식을 실시하였다 공여 신장은 60분의 warm ischemia를 유도한 후 UW solution으로 관류하고 24시간동안 냉장보관하여 자가이식하였으며, 반대쪽 신장은 적출하였다. 술 후 7일동안 혈청 creatinine치를 측정하였다 2차실험으로, 12마리의 Beagle견을 사용하여 4시간의 reperfusion 후 조직학적 변화와 myeloperoxidase의 활성을 조사하였다. 각 실험의 대조군은 생리 식염수를,비교군은 TBC1269 (selectin inhibitor)를 신장 적출 전과 신장이식 수술 후 reperfusion 직전에 각각 투여하였다. 혈청 creatinine은 신장이식후 급격히 증가 하였으나, 두군 사이에 유의적인 차이는 없었다. 신장피질의 백혈구 침윤은, 4시간 reperfusion후 생리식염수를 투여받은 군에서 2배의 유의적인 증가를 보였다. 그러나, TBC 1269로 처리한 군에서는 백혈구의 침윤이 유의적인 억제를 보였으며, 허혈에의한 조직학적 변화도 유의적으로 적었다. 개의 신장이식 수술에서 Selectin의 차단은 warm renal ischemia에서 기인된 손상을 개선하지는 못하나, 백혈구의 침윤을 억제하므로 delayed graft function과 관련된 술 후 염증반응의 초기화를 억제하는 효과가 있는 것으로 사료된다.

• 한국임상수의학회지
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• 제25권3호
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• pp.165-169
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• 2008

Renal ischemia-reperfusion (I/R) injury is great clinical important because viability of the organ depends on the tolerance to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of premedicated ascorbic acid alone in I/R injury model induced by cross-clamping of renal vessels. In the rabbit models, 2-4 kg New Zealand white rabbits were subjected to 30 minutes of warm unilateral renal ischemia followed by removal of contralateral kidney and then divided into five groups, control (2) arid treatment groups (3). In control group 1, the rabbits only received right nephrectomy. In control group 2, the rabbits received I/R on left kidney after the right nephrectomy. In treatment group 1, the rabbits received ascorbic acid 50 mg/kg IV before the operation. In treatment group 2, the rabbits received ascorbic acid 100 mg/kg IV before the operation. In treatment group 3, the rabbits received ascorbic acid 200 mg/kg IV before the operation. Blood samples were collected from these rabbits for measurement of kidney function tests at the 0, 1 st, 3rd and 7th day and antioxidant enzyme( SOD, GSHPx, CAT) at 24 hours. Kidney function tests (serum creatinine and BUN) showed a significant difference between group 2 and group 4, 5. Activity of antioxidant enzymes in plasma were significant decrease in group 4, 5 compare to group 2. The result of this study suggested that the exogenous ascorbic acid had a role of attenuation of renal I/R injury in rabbit model.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.413-423
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• 2021

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

• Preventive Nutrition and Food Science
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• 제17권2호
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• pp.101-108
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• 2012

Interruption or prolonged reduction and subsequent restoration of blood flow into the kidney triggers the generation of a burst of reactive oxygen species (ROS), leading to injury in the tubular epithelial cells. In this study, we determined whether methanol extract of goat's-beard (Aruncus dioicus) (extract) could prevent this ischemia/reperfusion injury. When in vitro radical scavenging activity of the extract was measured using a DPPH radical quenching assay, the extract displayed slightly lower activity than ascorbic acid. One hour after administration of the extract (400 mg/kg) by intraperitoneal injection in rats, renal ischemia/reperfusion injury was generated by clamping the left renal artery for forty minutes, followed by 24 hr restoration of blood circulation. Prior to clamping the left renal artery, the right renal artery was removed. Compared with the vehicle-treated group, pretreatment with the extract significantly reduced the tubular epithelial cell injury by 37% in the outer medulla region, and consequently reduced serum creatinine concentration by 39%. Reduction in the cell injury was mediated by attenuation of Bax/Bcl-2 ratio, inhibition of caspase-3 activation from procaspase-3, and subsequent reduction in the number of apoptotic cells. Thus, goat's-beard (Aruncus dioicus) might be developed as a prophylactic agent to prevent acute kidney injury.

• International Journal of Stem Cells
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• 제16권2호
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• pp.168-179
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• 2023

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods and Results: Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions: The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

• 한국임상수의학회지
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• 제26권5호
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• pp.441-444
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• 2009

허혈/재관류 손상은 장기이식 분야에서 해결해야 할 주요 문제점으로 알려져 있다. 본 연구에서는 대퇴 동,정맥 부위에서 기존의 혈관 문합법 대신 맥관 connector를 이용하여 간단하면서 효과적인 체외 재관류 모델을 개발하였기에 소개하고자 한다. 개발된 모델이 허혈/재관류 손상연구에 효과적인지 알아보기 위해 혈액 동력학적 평가와 신장의 재관류 후 손상 양상을 분석하였다. 기존의 재관류 모델에서 사용되는 문합 부위인 복강 대동맥의 혈압과 본 연구에서 재관류 부위로 활용된 대퇴동맥의 혈압은 유의적 차이가 없었다. 허혈 손상 후 재관류 효과를 알아보기 위해 미니돼지에서 적출한 신장을 HTK 용액에 24, 48시간 동안 각각 저온보관 후 대퇴부에 이식하여 재관류 한 결과, 신장의 재관류까지 수술시간은 평균 $7.0{\pm}1.1$분 소요되었으며, 3시간 재관류 후 재관류 손상 정도는 저온보관시간에 따라 증가되는 것이 확인되었다. 이는 개발된 모델이 맥관 문합 없이 간단한 관류방법이면서도 기존의 복잡한 수술에 의한 재관류 방법과 유사한 손상 모델을 만들 수 있는 효과적인 허혈/재관류 동물모델이라는 것을 의미한다. 따라서 본 연구에서 개발한 신장 재관류 모델은 초기 허혈/재관류 손상 연구와 장기이식에서 이식면역연구에 효과적인 모델이라 사료된다.

• 한국임상수의학회지
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• 제26권3호
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• pp.200-204
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• 2009

This study was performed to evaluate the effects of reduced L-glutathione on the oxidant/antioxidant status(superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GPx), protein carbonyl and lipid hydroperoxide(LPO) concentration), renal function(blood urea nitrogen(BUN) and serum creatinine levels), and microscopy of renal tissues in pigs undergoing unilateral renal ischemia-reperfusion(I/R). Sixteen Landrace and Yorkshire mixed-breed pigs were divided randomly into two groups: untreated control group and reduced L-glutathione-treated group(4 mg/kg IV). Each group had 8 pigs. Pigs were unilaterally nephrectomized and the kidney was subject to 30 min of renal pedicle occlusion. Blood samples for biochemical assay were collected on days 1, 3, 5, 7, and 14 post nephrectomy. Renal I/R injury were evaluated histopathologically by the microscopic observation of renal tissue sections and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as SOD, GPx, CAT, protein carbonyl and LPO were measured. The elevation of creatine and BUN levels was lower in the treated group, compared with the control group. The activities of antioxidant-enzyme were higher in the treated group, compared with the control group. In histological findings, the severity of damage in the reduced L-glutathione treated group was less when compared to the control group.

• 대한한의학방제학회지
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• 제29권1호
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• pp.33-44
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• 2021

Renal ischemia-reperfusion injury(IRI), an important cause of acute renal failure (ARF), cause increased renal tubular injury. Jesaeng-sinkihwan (JSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon (方藥合編)". JSH has been used for treatment of diabetes and glomerulonephritis with patients. Here we investigate the effects of Jesaeng-sinkihwan (JSH) in a mouse model of ischemic acute kidney injury. The animals model were divided into four groups at the age of 8 weeks; sham group: C57BL6 male mice (n=9), I/R group: C57BL6 male mice with I/R surgery (n=9), JSH Low group: C57BL6 male mice with surgery + JSH 100 mg/kg/day (n=9) and JSH High group: C57BL6 male mice with surgery + JSH 300 mg/kg/day (n=9). Ischemia was induced by clamping the both renal arteries during 25 min, and reperfusion was followed. Mouse were orally given with JSH (100 and 300 mg/kg/day during 3 days after surgery. Treatment with JSH significantly ameliorates creatinine clearance(Ccr), Creatinine (Cr) and blood urea nitrogen(BUN) in obtained plasma. . Treatment with JSH reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). JSH also reduced the periodic acid schiff (PAS) staining intensity and picro sirius red staining intensity in kidney of I/R group. These findings suggest that JSH ameliorates tubular injury including renal dysfunction in I/R induced ARF mouse.

• 한국임상수의학회지
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• 제27권5호
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• pp.553-558
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• 2010

본 연구의 목적은 개의 신장 절개술 모델에서 ascorbic acid를 전처치 하거나 관주 및 흡인시에 있어서, 허혈/재관류 손상의 감소와 신장 기능의 회복에 대한 효과를 평가하는데 있다. 성숙 잡종견 9두에서 신장절개술을 실시하였으며, hepa-saline 관주 및 흡인군와 ascorbic acid로 전처치 한 후 hepa-saline 관주 및 흡인한 군을 각각 실험군 1, 2로 놓았다. 신기능 검사와 항산화 효소 검사를 위해 신장절개술 후 0, 1, 3, 5, 7일에 혈액 샘플을 채취하였다. 그리고 7일 후 TNF-alpha, INF-gamma 검사를 위해 신장을 적출 보관하였다. 신장의 기능 검사에서 처치군 1과 2는 재관류 후 3, 5 그리고 7일째에 대조군과 비교하여 유의성 있게 감소 하였으며(p < 0.05), 처치군 2는 재관류 후 3일째에서 처치군 1과 비교하여 유의성있게 감소하였다(p < 0.05). 혈장에서의 항산화 효소의 활성치는 처치군 1과 2는 재관류 후 3, 5 그리고 7일째에 대조군과 비교하여 유의성 있게 증가 하였으며(p < 0.05), 처치군 2는 재관류 후 3일째에서 처치군 1과 비교하여 유의성있게 증가하였다(p < 0.05). TNF-alpha는 감소하고, INF-gamma는 증가하였다. 본 연구의 결과 신장의 관주 및 흡인의 과정은 신장의 관주 및 흡인의 과정은 신장의 허혈 및 재관류 손상을 감소 시키는 데에 효과가 있음을 시사하며, 또한, 외인성 ascorbic acid의 투여는 개의 신장 절개술에서 허혈 및 재관류의 손상을 감소시키며 신기능의 회복에 효과가 있음을 시사한다.

• 한국임상수의학회지
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• 제25권4호
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• pp.257-262
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• 2008

신장의 허혈-재관류 손상은 수술하는 동안 부득이하게 발생하는 허혈-재관류 손상에 대한 이식조직의 내성에 따라 이식된 장기의 생존력이 달려있기 때문에 임상적으로 아주 중요하다. 본 연구의 목적은 신장 혈관을 차단하여 유발한 허혈-재관류 모델에서 관류-흡인의 효과를 알아보고자 실시하였다. 신기능과 항산화 효소를 검사하기 위해 혈액 샘플을 채취하였고 신장내 동맥의 혈류저항을 측정하였다. 14일째 신장을 절제하여 조직검사를 실시하였다. 신기능(Cr, BUN)은 처치군에 비해 비처치군에서 유의성 있는 상승을 보였다. 신장내 혈류 저항은 두 그룹 사이에 유의성이 없었다. 항산화 효소 활성은 대조군에 비해 비처치군에서 유의성 있는 감소를 보였으나, 처치군에서는 대조군과 유의성이 없었다. 조직검사 결과에서도 처치군이 비처치군에 비해 적은 조직손상을 보였다. 이러한 결과는 관류-흡인 과정이 신장의 허혈-재관류 손상을 감소시키는데 유용한 단계임을 시사한다.