당뇨 흰쥐 요도에서 Nitric Oxide Synthase 함유신경의 변화와 요도주위 섬유화의 의의
The Significance of Periurethral Fibrosis and the Change of Nitric Oxide Synthase Containing Nerves in the Urethra of Diabetic Rats
정연구, 유형상, 권용현, 박창신, 임우성, 류지간, 이택, 윤상민,
소속 상세정보
정연구 ( Chung Yeun-Goo )
인하대학교 의과대학 비뇨기과학교실
유형상 ( You Hyung-Sang )
유비뇨기과의원
권용현 ( Kwon Yong-Hyun )
인하대학교 의과대학 약리학교실
박창신 ( Park Chang-Shin )
인하대학교 의과대학 약리학교실
임우성 ( Lim Woo-Sung )
인하대학교 의과대학 비뇨기과학교실
류지간 ( Ryu Ji-Kan )
인하대학교 의과대학 비뇨기과학교실
이택 ( Lee Tack )
인하대학교 의과대학 비뇨기과학교실
윤상민 ( Yoon Sang-Min )
인하대학교 의과대학 비뇨기과학교실
KMID : 0358320070480101050
Abstract
당뇨병은 우리나라에서 식생활 방식의 서구화로 유병률과 발병률이 지속적으로 증가하고 있으며, 현재 심각한 사회문제로 대두되고 있다.1,2 가장 초기 합병증은 감각신경의 마비이며, 실제로 상당수의 환자들이 자신의 배뇨장애를 전혀 인지하지 못해서 현재까지 보고된 당뇨병성 방광병증의 발병률에 대한 연구결과도 실제보다 과소평가되어 있다.3 이는 당뇨성 방광병증의 발병률이 여러 연구에서 25%에서 85%까지 매우 큰 폭의 변이를 보인다는 점에서도 알수 있다.1,2 최근 연구에서는 당뇨병성 신경병증 환자의 약
80% 이상에서 요역동학검사에서 방광기능이상을 보인 것으로 나타나 당뇨병성 방광병증의 매우 높은 유병률을 알 수 있다.4
Purpose:We have previously demonstrated that increased urethral resistance was more prominent in diabetic rats than in controls. This may result from a compressive obstruction such as damage of the urethral nerve containing nitric oxide. Another possible cause for urethral obstruction could be a constrictive obstruction such as a periurethral fibrosis. In the present study, we investigated the changes in the expression of nitric oxide synthase(NOS) isoforms(compressive obstruction) and collagen subtypes (constrictive obstruction) in the urethral tissues of non-insulin dependent diabetic rats.
Materials and methods: Thirty-six male Sprague-Dawley rats(18 diabetic rats and 18 control rats), bred from birth, were included in this study. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin(90mg/kg) on the second day after birth. Urethral tissues were harvested at 12, 24 and 36 weeks after induction of diabetes and were stained for neuronal NOS(nNOS) and Masson trichrome. We also performed reverse transcriptase-polymerase chain reaction or Western blot analysis to evaluate mRNA or protein expression of NOS isoforms and collagen subtypes in the urethral tissues.
Results:Immunohistochemical staining and Western blot analysis of nNOS revealed that the immunoreactivity and nNOS expression in the urethra was lower in the diabetic rats than in the controls. The Masson trichrome staining showed that there was urethral fibrosis in the diabetic rats. The mRNA or protein expression of collagen subtypes, especially type I collagen, were higher in the diabetic rat urethra than in the controls.
Conclusions:These data suggest that the increased urethral resistance in diabetic rats may be attributable to a decrease in the urethral nNOS expression and an increase in collagen content. Urethral dysfunction as well as a cystopathy may play an important role in the pathogenesis of diabetes- induced voiding dysfunction. (Korean J Urol 2007;48:1050-1057)
키워드
Diabetic cystopathy;Urethra;Nitric oxide;Collagen
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