초록 ▼

항암제 시스플라틴 처치로 인하여 유발된 신독성에 대한 글루타민의 신장 보호 효과는 다음의 여러 과정에서 나타났다.
1)신장기능: 신기능 저하를 통계적으로 의미있게 억제함을 BUN과 Cr level의 변화를 통하여 검증.
2) 조직손상: 시스플라틴으로 인하여 야기된 신장의 조직병리학적 변화 (severe casts, tubular necrosis, loss of brush border, intratubular debris)도 글루타민 처치로 인하여 현저히 감소.
3) 조직 내 세포사멸: 조직 내 세포사멸에도 관여하여

항암제 시스플라틴 처치로 인하여 유발된 신독성에 대한 글루타민의 신장 보호 효과는 다음의 여러 과정에서 나타났다.
1)신장기능: 신기능 저하를 통계적으로 의미있게 억제함을 BUN과 Cr level의 변화를 통하여 검증.
2) 조직손상: 시스플라틴으로 인하여 야기된 신장의 조직병리학적 변화 (severe casts, tubular necrosis, loss of brush border, intratubular debris)도 글루타민 처치로 인하여 현저히 감소.
3) 조직 내 세포사멸: 조직 내 세포사멸에도 관여하여 TUNEL 양성반응과 caspase-3의 cleavage가 글루타민 처치군에서 현저히 감소.
4)산화적 스트레스: GSH level과 MDA의 발현 변화를 통하여 글루타민이 시스플라틴으로 증가된 신장조직 내 산화적 스트레스를 감소.
5)염증반응I: 조직상에서의 MCP-1, ICAM-1 양성반응의 세포들의 수가 글루타민 처치군에서 현저히 감소.
6)염증반응II: NF-kB 경로를 담당하는 IKB-a의 인산화 형태의 단백질수준과 COX-2의 발현이 현저히 감소.
7) EMT: Epithelial-mesenchymal transition (EMT)에 관련된 E-cadherin의 시스플라틴에 의한 감소된 양성반응이 글루타민 처치로 인하여 감소가 억제됨.

Abstract ▼

Background: Cisplatin is a chemotherapy drug and nephrotoxin that induces acute kidney injury (AKI). Cisplatin-induced AKI depends on several signaling pathways leading to apoptosis in tubular epithelial cells. Several investigators have demonstrated that cisplatin induces oxidative stress in renal

Background: Cisplatin is a chemotherapy drug and nephrotoxin that induces acute kidney injury (AKI). Cisplatin-induced AKI depends on several signaling pathways leading to apoptosis in tubular epithelial cells. Several investigators have demonstrated that cisplatin induces oxidative stress in renal epithelial cells primarily by decreasing antioxidant enzyme activity and depleting intracellular concentrations of glutathione. Numerous studies have now documented the beneficial effects of various antioxidants in cisplatin-induced nephrotoxicity. Glutamine is a nonessential amino acid and substrate for the synthesis of glutathione, the most abundant intracellular thiol and antioxidant. Thus, the antioxidant properties of glutamine could contribute to beneficial effects in cells experimentally and glutamine might play an important role in protecting cells from apoptosis induced by different stimuli.
Goals: In the present study, we sought to evaluate the protective effect of glutamine on cisplatin-induced AKI. Methods: Male Sprague Dawley rats (200-230 g) were divided into control, glutamine, cisplatin, and cisplatin plus glutamine groups. The control group received a single injection of saline, intraperitoneally. The glutamine group received a single subcutaneous injection of glutamine (1 g/kg body weight). The cisplatin group received a single intraperitoneal injection of cisplatin (10 mg/kg body weight) and then an equal volume of phosphate-buffered saline instead of glutamine. The cisplatin plus glutamine group first received cisplatin, and then glutamine at day 1 after cisplatin injection. All animals were sacrificed at day 3 after cisplatin injection. Blood and tissue samples were collected for analysis of renal function and tissue damage. Results: 1) Glutamine protects against renal functional impairment induced by cisplatin. 2) Reduced cisplatin-induced renal tubular injury (severe casts, tubular necrosis, loss of brush border, intratubular debris)following glutamine administration. 3) Reduced cisplatin-induced renal tubular apoptosis (reflected as TUNEL staining and cleavage of caspase-3) following glutamine administration. 4) Decreased oxidative stress (confrimed by tissue GSH level and tisssue MDA expression level) in the kidney tissue. 5) Ameliorated renal inflammation-related molecules (IkB-alpha, COX-2, ICAM-1, MCP-1) expression. 6)Reduced epithelial mesenchymal transition by decreased immunofluorescence staining for E-cadherin in HK-2 cells. Conclusion: Because cisplatin has multiple cellular targets, blocking its effect on a single target may only provide partial protection against nephrotoxicity. For this reason, the broad mechanism of action of glutamine treatment may be particularly advantageous in the treatment of cisplatin-induced AKI. Prospects: The present study provides a new role for glutamine in decreasing cisplatin-induced nephrotoxicity and glutamine could be a useful treatment for patients with cisplatin-induced acute kidney injury and cancer.

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 보고서 요약서 ... 3
• 요 약 문 ... 4
• SUMMARY ... 5
• 6. 연구 성과 실적 및 향후 계획 ... 6
• 6.1 총괄연구개발과제의 연구성과 실적 및 향후 계획 ... 6
• 6.2 연구성과 유형별 세부 내역 ... 7
• II. 총괄연구과제 연구결과 ... 10
• 1. 연구개발과제의 배경 및 필요성 ... 11
• 2. 국내외 기술개발 현황 ... 14
• 3. 연구개발과제의 추진체계 ... 15
• 4. 연구개발수행 내용 및 결과 ... 17
• 5. 목표달성도 및 관련분야 기여도 ... 27
• 6. 향후 연구성과 추진 계획 ... 28
• 7. 연구개발결과의 파급효과 ... 28
• 8. 연구개발결과의 활용계획 ... 29
• 10. 참고문헌 ... 30
• IV. 첨부서류 ... 32
• 끝페이지 ... 45