대동맥협착 고혈압 백서에서 산화환원조절단백 APE1/Ref-1의 발현변화
Redox Regulating Protein APE1/Ref-1 Expression is Increased in Abdominal Aortic Coarctation-induced Hypertension Rats
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연구배경: 본 연구에서는 대동맥협착 고혈압 동물모델을이용하여 혈압변화 시 산화환원조절단백-1(apurinic/apyrimidinic endonuclease 1/redox factor-1, APE1/Ref-1)의발현변화를 규명하고자 하였다. 방법: 실험동물은 Sprague-Dawley 백서를 이용하였으며 대동맥협착군, 협착 제거군 및 Sham 대조군 및 정상군으로 나누었다. 혈관내피세포의 기능은 내피 의존성 이완반응으로 확인하였다. 활성산소종 및 지방과산화 정도는 lucigenin 발광반응과 thiobarbituric acid-reactive substances 방법을 이용하였으며 APE1/Ref-1의 발현은 Western blot 및 면역조직염색방법을 이용하여 확인하였다. 결과: 대동맥협착군의 수축기/이완기혈압은 171/114 증가를 보였다. 대동맥협착군에서 내피 의존성 이완반응은 현저히 감소하였으며, 활성산소종 및 지방과산화 정도는 증가하였다. 혈압상승에 의하여 감소된 내피 의존성이완반응은 대동맥협착 제거에 의하여 정상으로 회복되었다. APE1/Ref-1 발현은 대동맥협착군의 대동맥 및 신장조직에서 증가하였다. 대동맥조직에서 APE1/Ref-1의발현증가는 대동맥협착 제거에 의하여 회복양상을 보였으나 신장조직에서는 회복되지 않았다. 결론: 연구결과를 종합해 볼 때 산화환원조절단백 -1(APE1/Ref-1)은 혈압증가에 의하여 발현이 증가됨으로써고혈압의 바이오마커 가능성이 제시되었다. 고혈압 동물에서 나타난 내피 의존성 이완반응의 감소현상은 대동맥협착 제거한 1주 후 회복되어 내피 의존성 이완반응의 가역성을 확인하였다.
Abstract
Background: Aim of study is designed to investigate whether apurinic/apyrimidinic endonuclease-1/redox factor-1(APE1/Ref-1) expression is changed in abdominal aortic coarctation models. Methods: Male Sprague–Dawley rats were randomly assigned with abdominal aortic coarctation, repaired group, sham, and control groups. Endothelial function was assessed with endothelium-dependent relaxations. Detection of superoxide anion and lipid peroxidation was performed by lucigenin chemiluminescence and thiobarbituric acid-reactive substances assay. APE1/Ref-1 expression was measured with Western blot and immunohistochemistry. Results: In anesthetized condition, the abdominal aortic coarctation rats showed hypertension as systolic/diastolic arterial pressure of 171/114 mm Hg, compared with 114/94 mm Hg of control. Endothelium-dependent relaxations were significantly impaired in the aortic coarctation which was recovered in 1 week after coarctation repair. Superoxide production and lipid peroxidation were elevated in aortic coarctation rats. In immunohistochemistry, APE1/Ref-1 expressions were increased at aorta and kidney in aortic coarctation rats. Increased APE1/Ref-1 expression in aorta was recovered by repair of coarctation. Conclusions: Taken together, it suggests that APE1/Ref-1 expression was increased in aortic coarctation-induced hypertensive rats, suggesting a biomarker for hypertension. Impaired endothelium dependent relaxation in the aortic coarctation can be modulated by repair of coarctation or the modulation of blood pressure.
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