신기능 장애모델에서의 B-Lapachone의 영향 = B-Lapachone effect in ZSF1 rat model

다국어 초록 (Multilingual Abstract)

Background: Metabolic syndrome has been identified as powerful predictors of chronic
kidney disease. However, pharmacological approaches to attenuate metabolic syndrome
and its renal sequelae have been limited. This study aimed to determine the effect of β
-lapachone ( L), a NAD(P)H oxidation stimulator, on renal dysfunction β in ZSF1 Rats, a
well characterized animal model of the metabolic syndrome with concomitant kidney
sequelae.
Methods: ZSF1 rats were treated, beginning at 21 weeks of age, for 19 weeks with
vehicle or βL with the monitoring body weight and food intake. After treatment, plasma
glucose, insulin, and adipokines were measured and renal function including kidney
hypertrophy, urine albumin excretion, and creatinine clearance were also determined. To
test the antifibrotic efficacy of βL, we examined whether βL treatment can affect renal
histology of ZSF1 rat and fibrogenic gene expression in mesangial cell.
Results: βL significantly reduced body weight (control vs βL, 596.6 ±50.0 vs 520.5 ± 40.1
g, p< 0.05) and fasted plasma glucose levels (control vs βL, 10.38 ± 0.39 vs 5.78 ± 0.55
mmol/L, p<0.01). βL treatment ameliorated the dyslipidemia and increased serum
adiponectin level. Deterioration in renal function was retarded as evident from albumin to
creatinine ratio (albumin/creatinine ratio, control vs βL, 1.16±0.31 vs 0.22±0.03, p<0.05)
and kidney hypertrophy (kidney weight/tibia length, control vs βL, 119.5 ± 5.5 vs 80.9 ±
4.0 g/mm, p<0.05). These changes were accompanied by decreased renal fibrosis in
histopathology. This finding was consistent with the decreased gene expressions related
renal fibrosis (PAI-1, fibronectin, and collagen-1) stimulated by TGF-β in rat kidney
mesangial cells.
Conclusion: These findings suggest that βL resolves the component of metabolic
syndrome, glomerular dysfunction, and renal fibrosis associated with metabolic syndrome.

목차 (Table of Contents)

• I. 서론 -------------------------------------- 1
• 1. 대사성 증후군 신장 기능 이상 ----------------- 1
• 2. 만성 신장 질환 동물 모델 -------------------- 7
• 3. β-Lapachon ------------------------------ 9
• 4. 연구 목적 -------------------------------- 11
• II. 재료 및 방법 ------------------------------ 12
• 1. 동물실험 --------------------------------- 12
• 2. 혈액분석 --------------------------------- 12
• 3. 혈청 사이토카인 측정 ----------------------- 13
• 4. 크레아티닌 청소율 ------------------------- 13
• 5. 신장 조직학 분석 -------------------------- 13
• 6. 세포 배양 -------------------------------- 14
• 7. Western blot ----------------------------- 14
• III. 결과 및 고찰 ----------------------------- 16
• 1. 결과 ----------------------------------- 16
• βL의 ZSF-1 rat 에서의 몸무게 증가 및 장기별 비대화 효과16 -
• ZSF-1 rat에서의 βL이 대사성 증후군에 미치는 영향 ---16
• βL의 ZSF-1 rat 모델에서의 신장 기능에 미치는 영향 17
• βL의 ZSF-1 rat 모델에서의 신장 섬유화 영향 ---- 18
• TGFβ 신호전달에 의해 유도되는 신장 세포 섬유화에 βL
• 미치는 영향 ------------------------------18
• 2. 고찰 -------------------------------- 20
• IV. 한국어 요약 --------------------------- 29
• V. 참고문헌 ------------------------------ 30
• 한글 초록 ---------------------------------- 38