Alcohol linked to enhanced angiogenesis in rat model of choroidal neovascularization
Alcohol linked to enhanced angiogenesis in rat model of choroidal neovascularization
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DOI：
10.1111/j.1742-4658.2006.05163.x
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发表时间：
2006-04-01
期刊：
影响因子：
5.4
通讯作者：
Bora, NS
中科院分区：
文献类型：
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作者：
Bora, PS;Kaliappan, S;Bora, NS
渗出性（即湿性）年龄相关性黄斑变性（AMD）的病理并发症之一是脉络膜新生血管形成（CNV）。本研究的目的是调查慢性和重度饮酒是否影响大鼠模型CNV的发展。酒精的氧化代谢在眼睛中是最小的或不存在的，因此乙醇通过非氧化途径代谢形成脂肪酸乙酯（FAEE）。从棕色挪威（BN）大鼠脉络膜中纯化脂肪酸乙酯合酶（FAEES）。纯化的蛋白质大小为60 kDa，针对该蛋白质产生的抗体在western blot上显示单一条带。正常饮食的BN大鼠被喂食酒精10周。对照组大鼠喂以水和常规饮食，配对喂养的对照组大鼠喂以常规饮食、水和葡萄糖。我们发现，FAEES活性增加4.0倍，在脉络膜中的酒精治疗大鼠与对照组相比。10周酒精喂养大鼠脉络膜中产生的乙酯量是1周酒精喂养大鼠的7.4倍。乙酯的积累增加与细胞周期蛋白E和细胞周期蛋白E/CDK 2的表达增加3.0倍有关;然而，细胞周期蛋白激酶抑制剂p27 Kip的水平没有变化。乙酯积累的增加也与脉络膜中APN表达降低3.0倍有关。我们还发现，在酒精喂养的大鼠中，CNV的大小增加了28%。因此，我们的研究表明，慢性，大量的酒精摄入与脉络膜中乙酯的积累增加和激光治疗引起的CNV恶化有关。这些结果可能提供深入了解之间的联系大量饮酒和渗出性AMD。
One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.