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당뇨성 미세단백뇨 발생기전에 있어서 Oxidative stress의 역할

Title
 당뇨성 미세단백뇨 발생기전에 있어서 Oxidative stress의 역할 
Other Titles
 (The) role of oxidative stress in development of diabetic microalbuminuria 
Issue Date
1993
Publisher
 연세대학교 대학원 
Description
의학과/박사
Abstract
[한글] Oxidative stress가 당뇨병에 수반되는 이차적 질환의 공통 발생기전이 될 것이라는 가설을 토대로, 본 연구에서는 당뇨성 콩팥 질환의 조기 지표인 미세단백뇨 발생에도 oxidative stress가 관여하는지 검색하고자 하였다. 흰쥐 정맥으로 streptozotocin 50mg/kg을 투여하여 실험적 당뇨를 유도한 후 microalbuminuria가 수반될 때, 지질파산화물과 8-hydroxydeoxyguanosine을 oxidative stress의 지표로서 정량하여 비교하였다. 더 나아가 항단백뇨효과가 있는 captopril의 항산화제로서의 역할을 알아보고자 화학적 구조가 다른 angiotensin 전환효소 억제제인 enalapril 및 항산화제인 vitamin E가 지질과산화에 미치는 영향을 비교하였을 때, 1. Streptozotocin 투여에 의하여 당뇨가 유발된 흰쥐는 대조군에 비하여 사구체 여과율은 의의있게 변동되지 않았으나 albumin 배설은 의의있게 증가하였다. 2. 당뇨 유발로 요중 지질과산화물은 현저하게 증가하였고, 이 증가의 일부는 근위세뇨관에서 형성되는 지질과산화물 뿐아니라 혈장 지질과산화물 증가에도 기인하였다. 3. 콩팥 조직내 8-hydroxydeoxyguanosine이 당뇨 유발로 의의있게 증가하였다. 4. Insulin 투여로 당뇨 유발에 의한 일반 특성및 지질과산화물과 8-hydroxydeoxyguanosine 함량 변동이 개선되었다. 5. Angiotensin 전환효소 억제제중 항산화기인 -SH기를 함유한 captopril 뿐 아니라 함유하지 않은 enalapril 모두 장기투여 했을 때 당뇨쥐에서 관찰되는 microalbuminuria를 개선하였고, 지질과산화물 증가를 억제하였다. 6. 식이를 제한하지않은 상태에서 vitamin E를 장기투여 하더라도 당뇨쥐에서 관찰되는 지질과산화물 증가에 영향을 주지 않았고 microalbuminuria에도 영향이 없었다. 본 연구의 결과 당뇨 흰쥐의 콩팥 조직내 oxidative stress가 증가되어 있음을 알 수 있었고,captopril의 항단백뇨 기전에는 angiotensin 형성 억제와 관련된 아직 규명되지 않은 항산화작용도 관여하고 있으리라 추측되는 바이다. The role of oxidative stress in development of diabetic microalbuminuria Keun Hwang Department of Medical Scoence, The Graduate School Yonsei University (Directed by Professor Kyung Hwan Kim) Based on the recent hypothesis that oxidative stress may be a common cause of diabetic complications, the present study examined possible involvement of oxidative stress in the process of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50mg/kg into the tail vein of male Sprague-Dawley rats. The levels of lipid peroxides and 8-hydroxydeoxyguanosine in tissues were determined as indices of the oxidative stress in diabeticrats exhibiting microalbuminuria. Furthermore the effects of captopril, enalapril and vitamin E on microalbuminuria and lipid peroxidation in diabetic rats were compared in order to evaluate whether captopril's antiproteinuric effect is due to anti-free radical activity depending on its sulfhydryl moiety. The results are summarized as follows; 1 . Streptozotocin-induced diabetic rats excreted significantly increased urinary albumin, compared to age-matched control rats. 2. Urinary lipid peroxides in diabetic rats were increased. The source of the urinary lipid peroxides may be the lipid peroxides from renal proximal tubules and/or from plasma. 3. Level of 8-hydroxydeoxyguanosine in the kidney of diabetic rats were also increased com-pared to control rats. 4. Insulin treatment ameliorated alterations in lipid peroxides and 8-hydroxydeoxyguanosine as well as general characteristics of diabetic rats. 5. Angiotensin converting enzyme inhibitor, whether it has sulfhydryl group or not, reduced higher levels of urinary excretion of albumin or lipid peroxides associated with diabetes. 6. Chronic administration of vitamin I without controlling of diet did not cause any significant effect on urinary excretion of lipid peroxides or albumin. Above results suggest that oxidative damage is closely related in the process of diabetic nephropathy, and antiproteinuric property of captopril may be due to undefined antioxidative activity related with inhibition of angiotensin converting enzyme.
[영문] Based on the recent hypothesis that oxidative stress may be a common cause of diabetic complications, the present study examined possible involvement of oxidative stress in the process of diabetic nephropathy. Experimental diabetes was induced by intravenous injection of streptozotocin 50mg/kg into the tail vein of male Sprague-Dawley rats. The levels of lipid peroxides and 8-hydroxydeoxyguanosine in tissues were determined as indices of the oxidative stress in diabeticrats exhibiting microalbuminuria. Furthermore the effects of captopril, enalapril and vitamin E on microalbuminuria and lipid peroxidation in diabetic rats were compared in order to evaluate whether captopril's antiproteinuric effect is due to anti-free radical activity depending on its sulfhydryl moiety. The results are summarized as follows; 1 . Streptozotocin-induced diabetic rats excreted significantly increased urinary albumin, compared to age-matched control rats. 2. Urinary lipid peroxides in diabetic rats were increased. The source of the urinary lipid peroxides may be the lipid peroxides from renal proximal tubules and/or from plasma. 3. Level of 8-hydroxydeoxyguanosine in the kidney of diabetic rats were also increased com-pared to control rats. 4. Insulin treatment ameliorated alterations in lipid peroxides and 8-hydroxydeoxyguanosine as well as general characteristics of diabetic rats. 5. Angiotensin converting enzyme inhibitor, whether it has sulfhydryl group or not, reduced higher levels of urinary excretion of albumin or lipid peroxides associated with diabetes. 6. Chronic administration of vitamin I without controlling of diet did not cause any significant effect on urinary excretion of lipid peroxides or albumin. Above results suggest that oxidative damage is closely related in the process of diabetic nephropathy, and antiproteinuric property of captopril may be due to undefined antioxidative activity related with inhibition of angiotensin converting enzyme.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117420
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
Yonsei Authors
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