20-羟基蛻皮激素抑制缺氧誘發因子-2α訊息路徑因IL-1β而導致軟骨細胞的凋亡

20-Hydroxyecdysone inhibit IL-1β- induced chondrocytes apoptosis via HIF-2α pathway

何欣蓉(Shin-Rong Ho)

指導教授 ： 許秀蘊

臺北醫學大學/藥學院/藥學院生技製藥產業碩士專班/碩士(2013年)

摘要

骨關節炎 ( Osteoarthritis; OA ) 是一種退化性的關節疾病，主要的特徵是關節軟骨退化，影響65歲以上三分之一的人口。現今臨床上用於治療骨關節炎的方式包含藥物及非藥物治療，但因骨關節炎的致病機制十分複雜，所以治療方式多著重於減少患病的疼痛及不適感，並未能夠完全有效預防及治療骨關節炎。科學家希望從其分子致病機制裡，可以找到一個生物標的來作為預防及治療骨關節炎的方向。
20-羟基蛻皮激素 ( 20-hydroxyecdysone ) 是植物牛膝( Achyranthes bidentata Blume; Amaranthaceae ) 的乾燥根 ( 又名「懷牛膝」) 中的一個化學成分。在文獻指出20-羟基蛻皮激素 ( 20-hydroxyecdysone = β-ecdysone = Ecd ) 在切除卵巢的老鼠中發現到具有抵抗骨質流失的功能，所以可以有效預防及治療因年紀或肥胖所造成的骨質疏鬆和骨關節炎。
缺氧誘發因子-2α ( Hif-2α ) 由Endothelial PAS domain protein-1 ( EPAS1 ) 轉錄而來，有文獻提到缺氧誘發因子-2α ( Hypoxia inducible factor; Hif-2α ) 在軟骨中的角色，使用相同的動物模型的實驗中都證明了Hif-2α會誘發骨關節炎的發生。
因此本實驗的主要研究目的是欲探討20-羟基蛻皮激素 ( 20-hydroxyecdysone ) 是否會透過抑制缺氧誘發因子-2α ( Hif-2α ) 路徑來降低因IL-1β ( Interleukin-1β ) 所導致軟骨細胞的凋亡，以了解骨關節炎的分子致病機制。實驗中發現到 Ecd對於軟骨具有保護的作用，可以抑制由IL-1β所造成的軟骨受損，推論此化合物可作為預防骨關節炎的方向。

關鍵字

20-羟基蛻皮激素,缺氧誘發因子-2α,骨關節炎

並列摘要

Osteoarthritis (OA) is a degeneration disease characterized by destruction of articular cartilage. The OA affects people who older than 60 years and more than one third of global population. As aging global population of each country for patients with health insurance also increased year by year, so for the treatment of this diseases is the most important issue.
In clinical, the treatment of osteoarthritis includes drugs and non-drug treatment and focuses on reducing the prevalence of pain and discomfort. Because the pathogenesis of osteoarthritis is very complicated, nowadays there are no fully effective in preventing and treatment of osteoarthritis. The scientists expect to discover the molecular pathogenesis of osteoarthritis and find a biomarker as the prevention and treatment of osteoarthritis direction.
20-hydroxyecdysone is a chemical composition of the dry root of the Achyranthes ( Achyranthes bidentata Blume; Amaranthaceae ). In some records, 20-hydroxyecdysone ( β-ecdysone/ Ecd ) has anti-osteoporosis in ovariectomized mice, so it can be effective in preventing and treating osteoporosis and osteoarthritis caused by obesity or age.
HIF-2α ( also designated endothelial PAS domain protein-1 or EPAS1) is a member of the basic helix-loop-helix/PAS transcription factor family. In two publications mentioned that the role of HIF-2α in the cartilage, HIF-2α would induce osteoarthritis in the same animal experiment model.
According to above reasons, the main purpose of this paper was to investigate whether the 20-hydroxyecdysone would inhibit cartilage cell apoptosis, caused by IL-1β though HIF-2α pathway, and also to understand the molecular pathogenesis of osteoarthritis. It was found that the 20-hydroxyecdysone has protective effect on cartilage and also suppresses cartilage damage caused by IL-1β. Therefore, this compound, 20-hydroxyecdysone, may be used as the direction of prevention of osteoarthritis.

並列關鍵字

20-hydroxyecdysone, Hif-2α, Osteoarthritis

參考文獻

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