당뇨병성 망막증에 있어서 Captopril에 의한 VEGF 발현 저하 효과
The Preventive Effect of Captopril on VEGF Expression in Streptozotocin-induced Diabetic Retiniopathy
2
조회
0
다운로드
0
인용
0
참고문헌
초록
당뇨병성 망막증의 당뇨병 합병증의 주요한 증상중의 하나로 망막의 구조적 기능적 변화를 초래한다. 레닌-안지오텐신 시스템 은 당뇨병성 망막증의 발병에 주요한 역할을 담당하며 angiotensin I을 angiotensin II로 전환하는 데 담당하는 안지오텐신 전환 효소 (ACE)는 레닌-안지오텐신 시스템의 주요한 요소이다. VEGF는 실명을 일으키는 당뇨병성 망막증의 신생혈관 생성에 관여하는 주요한 인자로 알려져 있다. 따라서 본 연구에서는 당 뇨병성 망막증의 발생 기전 중 하나로 최근 연구가 진행되고 있 는 VEGF의 발현과 안지오텐신 전환 효소 억제제를 이용한 VEGF 발현 억제효과의 규명을 통해 당뇨병성 망막증의 예방에 ACE 억제제가 효과가 있는지 ACE 억제제인 captopril을 이용하 여 알아보고자 하였다. 본 연구에서는 streptozotocin 처리시 혈청 내 VEGF 농도는 증가하였으나 captopril (65 mg/kg) 치료에 의해 감소하지 않았다. 망막에서 관찰한 결과 당뇨군에서 VEGF mRNA 및 단백질 발현이 증가하였으며, 안지오텐신 전환 효소인 capto-pril에 의해서 차단되는 것으로 나타났다. 결론적으로 captopril은 1형 당뇨에 있어서 망막의 VEGF 발현 억제를 통해 망막 보호효과를 나타내고 있음을 알 수 있었다.
Abstract
Diabetic retinopathy is one of major complications of diabetes mellitus, which is associated with the dysfunction of retina. It has been reported that the onset of diabetic retinopathy is related to the activation of renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE), which converts angiotensin I into angiotensin II, is a key component of RAS. Among many growth factors, vascualr endothelial growth factor (VEGF) is an important cytokine in the neovasculization of retina, which is a characteristics of diabetic retinopathy. However, the relationship between ACE and VEGF was not elucidated in diabetic retinopathy. Thus, this study was conducted to examine the protective effect of captopril, an ACE inhibitor, in the retina of streptozotocin (STZ)-treated diabetic rats. In present study, STZ-treated diabetic rats exhibited the increase of VEGF levels in serum and retina. The serum levels of VEGF in STZ-treated diabetic rats was not blocked by the treatment of captopril. However, the retina levels of VEGF in STZ-treated diabetic rats was blocked by the treatment of captopril, suggesting the local action of captopril in retina. Immunohistochemical analysis also revealed that the retina of STZ-treated diabetic rats manifested the increase of ganglion cell layers, outer nuclear layers, and inner nuclear layers, which were also prevented by the treatment of captopril. In conclusion, captopril prevented the expression of VEGF in the retina of STZ-treated diabetic rats.
참고문헌 (25)
- Bradford MM, "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein- dye binding", Anal Biochem, 72, pp.248~254 (1976)
- Brugts JJ, "Danser AH", Cardiology, 112(4), pp.303~312 (2008)
- Cavusoglu AC, "Vascular endothelial growth factor level in the serum of diabetic patients with retinopathy", Ophthalmol, 39(3), pp.205~208 (2007)
- Crawford TN, "Diabetic retinopathy and angiogenesis", Curr Diabetes Rev, 5(1), pp.8~13 (2009)
- Deshpande AD, "Epidemiology of diabetes and diabetes-related complications", Phys Ther, 88(11), pp.1254~1264 (2008)
- Ebrahimian TG, "Dual effect of angiotensin-converting enzyme inhibition on angiogenesis in type 1 diabetic mice", Arterioscler Thromb Vasc Biol, 25(1), pp.65~70 (2005)
- Ejaz S, "Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy", Diabetes Obes Metab, 10(1), pp.53~63 (2008)
- Gariano RF, "Retinal angiogenesis in development and disease", Nature, 438(7070), pp.960~966 (2005)
- Hansson GK, "Evidence for cell death in the vascular endothelium in vivo and in vitro", Am J Patho, 112(3), pp.278~286 (1983)
- Kim JH, "Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier breakdown in diabetic retinopathy", J Cereb Blood Flow Metab, 29(3), pp.621~628 (2009)
- Ko SH, "Clinical characteristics of diabetic ketoacidosis in Korea over the past two decades", Diabet Med, 22(4), pp.466~469 (2005)
- Korea Diabetes Association, "Diabetic retinopathy", Clinical Diabetes, 6(3), pp.216~219 (2005)
- Mycliwiec M, "The role of vascular endothelial growth factor, tumor necrosis factor alpha and interleukin-6 in pathogenesis of diabetic retinopathy", Diabetes Res Clin Pract, 79(1), pp.141~146 (2008)
- Nakanishi Y, "Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44", p42 mitogen-activated protein kinase, 2006, pp.83(5), 1108~1117
- Novo G, "The role of the renin-angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS", Br J Clin Pharmacol, 66(3), pp.345~351 (2008)
- Penn JS, "Vascular endothelial growth factor in eye disease", Prog Retin Eye Res, 27(4), pp.331~371 (2008)
- Rodriguez-Fontal M, "Ranibizumab for diabetic retinopathy", Curr Diabetes Rev, 5(1), pp.47~ (2009)
- Saint-Geniez M, "Endogenous VEGF is required for visual function: evidence for a survival role on muller cells and photoreceptors", PLoS ONE, 3(11), pp.e3554~ (2008)
- Sarlos S, "The renin-angiotensin system and the developing retinal vasculature", Invest Ophthalmol Vis Sci, 46(3), pp.1069~1077 (2005)
- Sugiyama T, "Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes", Exp Eye Res, 85(3), pp.406~412 (2007)
- Tikellis C, "Identification of angotensin converting enzyme 2 in the rodent retina", Curr Eye Res, 29(6), pp.419~427 (2004)
- van Bugenum MH, "Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy", Diabetol, 45, pp.203-209~ (2002)
- Wilkinson-Berka JL, "Angiotensin and diabetic retinopathy", Int J Biochem Cell Biol, 38(5), pp.752~765 (2006)
- Yoon KH, "Epidemic obesity and type 2 diabetes in Asia", Lancet, 368, pp.1681~1688 (2006)
- Zhang X, "Retinal expression of vascular endothelial growth factor is mediated by angiotensin type 1 and type 2 receptors", Hypertension, 43(2), pp.276~281 (2004)