초록 ▼

1. 신부전 환자에서 투석 방법에 따른 혈청 대사체 프로파일링 - 혈액투석 환자에게 inosine과 hypoxanthine이 축적됨.
2. 삼투압 변화 모델에서 쥐의 집합관 세포 내의 metabolome과 transcriptome의 통합 분석 - 감소된 삼투압이 유기 삼투질, 당, citric acid cycle 중간체, BCAA의 감소와 관련됨.
3. 만성 신부전 동물 모델의 혈액 내 대사체 프로파일링 연구 - 신장의 acid-base balance가 깨지고 산성화가 진행됨
4. 만성 신부전 환자의 혈액 내 대사체

1. 신부전 환자에서 투석 방법에 따른 혈청 대사체 프로파일링 - 혈액투석 환자에게 inosine과 hypoxanthine이 축적됨.
2. 삼투압 변화 모델에서 쥐의 집합관 세포 내의 metabolome과 transcriptome의 통합 분석 - 감소된 삼투압이 유기 삼투질, 당, citric acid cycle 중간체, BCAA의 감소와 관련됨.
3. 만성 신부전 동물 모델의 혈액 내 대사체 프로파일링 연구 - 신장의 acid-base balance가 깨지고 산성화가 진행됨
4. 만성 신부전 환자의 혈액 내 대사체 프로파일링 연구 - 신장의 병리 상태를 알 수 있는 GFR을 예측모델을 만듦.
5. 영상화 질량분석법을 이용한 furosemide 투입 rat 모델의 신장 내 대사체 변화 관찰 연구 - 신장 대사체의 공간적인 분포와 상대적 정량 분석에 성공적인 역할을 함.

Abstract ▼

Ⅳ. Results
1. Serum metabolite profiling study of patients with renal disease treated by dialysis
(1) Serum samples from patients with renal disease treated by haemodialysis (HD) and peritoneal dialysis (PD) were analyzed using 1H-NMR spectrometer.
(2) The profiling of serum metabolites bet

Ⅳ. Results
1. Serum metabolite profiling study of patients with renal disease treated by dialysis
(1) Serum samples from patients with renal disease treated by haemodialysis (HD) and peritoneal dialysis (PD) were analyzed using 1H-NMR spectrometer.
(2) The profiling of serum metabolites between HD and PD was influenced by dialysis-related processes.
(2) Inosine and hypoxanthine in patients on hemodialysis were accumulated in serum.
2. Integrated anaylsis of gene and metabolite in extracellular osmolality on kidney collecting duct
(1) Transcriptome and metabolome of primary cultured inner medullary collecting duct (IMCD) cells were analysed by 1H NMR, LC-MS amd gene chip.
(2) Integrated ana;ysis of the transcripome and metabolome revealed that decrease exreacellular osmolality was accociated with decreased levelas of organic osmolytes, glucose, intermediated of citric acid cycle, and branched chain amino acids (BCAA) in IMCD cells.
3. 1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease
(1) Plasma in rats with CKD induced by surgical reduction of the renal mass showed altered levels of acetate, citrate, lactate, formate, hydrobutyrate, alanine, glutamine and glutamate.
(2) These metabolic changed were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased proteon catabolism from muscle.
4. Metabolite profiling of serum from chronic kidney disease patients
(1) Serum from CKD patients with or without diabetes were analyzed using NMR.
(2) In the CKD patients, associations were seen with clinical characteristics, hyperglycemia, altered amino acid metabolism, accumulated uremic toxins, and dyslipidemia.
(3) Diabetes more strongly affected the metabolic signature during early stage CKD
(4) Serum metabolite profiles were successfully applied to the PLS regression model to predict the estimated glomerular filtration rate.
5. Metabolic study in the kidneys of furosemide-infused rats using imaging mass spectrometry
(1) To identify metabolic processes among the cortex (COR), outer medulla (OM), and inner medulla (IM), we examined the regional differences of the metabolites in the kidneys of furosemide-infused rats using a novel technology of the matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS).
(2) Extracts of COR, OM, and IM were analyzed by UPLC/Q-TOF-MS, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetyl carnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed.
(3) The changes of metabolites were further identified by MALDI-TOF/TOF and IMS.
Choline compounds were increased in COR and OM, but decreased in IM from furosemide rats. Carnitine compounds were increased in COR and IM, whereas carnitine and acetyl carnitine were decreased in OM. Betaine and GPC were decreased in OM and IM.
(4) Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney.

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 요약문 ... 4
• Summary ... 7
• Contents ... 10
• 목차 ... 11
• 제1장 연구개발과제의 개요 ... 12
• 제1절 연구개발의 목적 ... 12
• 제2절 연구개발의 필요성 및 범위 ... 12
• 제2장 국내외 기술개발 현황 ... 14
• 제3장 연구개발수행 내용 및 결과 ... 15
• 제1절 연구범위 및 연구수행방법 ... 15
• 제2절 연구내용 및 연구결과 ... 20
• 제4장 목표달성도 및 관련분야에의 기여도 ... 59
• 제1절 연구개발목표의 달성도 ... 59
• 제2절 관련 분야의 기술발전에의 기여도 ... 62
• 제5장 연구개발결과의 활용계획 ... 63
• 제1절 활용계획 ... 63
• 제2절 기대효과 ... 64
• 제6장 연구개발과정에서 수집한 해외과학기술정보 ... 65
• 제7장 연구시설·장비 현황 ... 68
• 제8장 참고문헌 ... 69
• 끝페이지 ... 70