運動禁藥－－缺氧誘導因子穩定劑

Doping: Hypoxia-Inducible Factor Stabilizers

紅血球生成刺激劑可使紅血球增加，隨著基因工程技術的進步，紅血球生成素的種類漸增，而以基因重組製造之人類紅血球生成素在臨床上主要是用來治療腎衰竭和許多因其他疾病所引起的貧血。不過濫用會有副作用產生，例如：紅血球發育不良症、中風、心臟衰竭等。由於紅血球生成刺激劑（ESA）具有顯著提昇有氧能力之效果，於運動競賽中使用會導致不公平情形，因此被世界運動禁藥管制機構（WADA）列為禁用物質。伴隨著檢測技術的進步，發現使用口服的缺氧誘導因子穩定劑（HIFs）後會增加血液中血紅蛋白的含量，故WADA在2011年的禁用清單上也將缺氧誘導因子穩定劑列為「胜肽性荷爾蒙、增長因子及其相關物質項-紅血球生成刺激劑類」之運動禁藥。本文將對缺氧誘導因子穩定劑的特性和臨床用途作介紹，並探討其在運動界被禁用的原因與檢測方法。

Erythropoiesis-stimulating agents (ESAs) can increase the number of erythrocytes. Since the advance of genetic engineering enables scientists to create a series of medical products, there are several ESAs currently available such as recombinant human erythropoietin (rEPO). In addition, rEPO has been shown significantly to facilitate the management of anemia of renal failure or other diseases. However, the abuse of rEPO causes the risk of pure red cell aplasia, stroke, and cardiac failure, etc. Due to athletes may use ESAs to improve the oxygen delivery to muscles, which directly improves their endurance capacities. The rEPO is prohibited both in and out of competition on the World Anti-Doping Agency (WADA) Code Prohibited List. Hypoxia-inducible factor stabilizers (HIFs) can activates erythropoietin and increase the concentration of blood hemoglobin and elevate the capacity of oxygen delivery. HIFs are prohibited under the category of 'Peptide hormones, growth factors and related substances' on the '2011 Prohibited List' of WADA. The current development and usage of HIFs and related small-molecule inhibitors, as well as the advanced technology platform for detection of these doping agents will be reviewed by this article.