전립선 비대증 환자에서 5-alpha reductase inhibitor 투여가 Cyclooxygenase-2의 발현에 미치는 영향

Abstract

[한글]

Cyclooxygenase (COX)는 arachionic acid가 prostaglandin과 eicosanoids으로 변환하는데 중요한 역활을 하는 효소이다. COX-1은 거의 모든 인체조직에서 발현이 되는 constitutive형이며 COX-2는 inducible 형태로 이것의 발현은 성장인자나 mitogen, cytokine 등과 같은 특별한 자극에 의한 반응으로 나타나며 전립선 비대증 (benign prostatic hyperplasia)에서 발현이 증가하는 것으로 알려져 있다. 본 연구는 5-α reductase inhibitor를 전립선비대증 환자에 투여하여 COX-2의 발현을 알아보고자 하였다.환자 50명을 대상으로 5-α reductase inhibitor를 적어도 3개월 이상 투여한 군을 실험군(n=20)으로 하였고 5-α reductase inhibitor투여하지 않은 군을 대조군(n=30)으로 하였으며 경요도전립선절제술로 전립선조직을 얻은 후 COX-2에 대한 면역형광염색을 시행하였다. 공초점현미경 및 영상분석기 (Zeiss LSM 5.0, Jena, Germany)를 이용하여 형광의 발현 정도를 평가하였다.전립선조직을 관찰하였을 때 COX-2는 luminal epithelium과 전립선기질에서 발현되었고 전립선기질보다는 luminal epithelium에서 강하게 발현되었다. 실험군의 발현이 대조군에 비해 통계학적으로 유의있게 감소되었다 (p<0.05).본 연구의 결과를 바탕으로 5-α reductase inhibitor가 전립선 비대증에서 COX-2의 down regulation을 일으키며 COX-2는 전립선 비대증의 proliferation에 중요한 역할을 하는 것으로 생각된다

[영문]Objectives: Cyclooxygenases are important enzymes in the conversion of arachidonic acid to prostaglandins and eicosanoids. Cyclooxygenase-1 (COX-1) is constitutively expressed in almost all human tissues. Cyclooxygenase-2 (COX-2) is the more inducible form and it has been thought that COX-2 is over-expressed in response to specific stimuli such as growth factors, mitogens and cytokines. The aim of this study is to determine the effect of 5-α reductase inhibitor on the expression of COX-2 in patients with benign prostatic hyperplasia (BPH).Patients and Methods: Fifty patients who had diagnosed with BPH were divided into two groups. The experimental group (n=20) was administrated 5 mg of the 5-α reductase inhibitor daily for at least 3 months, while the control group (n=30) was not administrated with the drug. Prostatic tissues were obtained from both control and experimental groups by transurethral resection of the prostate (TURP). Specimens were stained with mouse anti-human COX-2 monoclonal antibodies using immunofluorescence staining. The expression of COX-2 was analyzed with confocal microscope and an image analyzer.Results: COX-2 was expressed in the luminal epithelium and smooth muscle cells of BPH patients. COX-2 expression was found in the luminal epithelium than in the stroma. The control group showed stronger expression of COX-2 than that of experimental group (p<0.05).Conclusion: These results demonstrate that the 5-α reductase inhibitor down-regulates the expression of COX-2 in patients with BPH and suggest that COX-2 may play a role in the proliferation of prostatic tissue in patients with BPH