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標題: | 大豆異黃酮和天麻萃取物T1-11對酸引起的慢性肌肉疼痛所造成的影響 Effect of Soy Isoflavones Genistein and Gastrodia elata Extraction T1-11 on Acid-induced Chronic Muscle Pain |
作者: | Chia-Wen Wong 翁嘉文 |
指導教授: | 陳志成(Chih-Cheng Chen) |
關鍵字: | 肌肉,酸,疼痛過敏化,大豆異黃酮,T1-11, muscle,acid,hyperalgesia,genistein,T1-11, |
出版年 : | 2012 |
學位: | 碩士 |
摘要: | 慢性肌肉疼痛在世界各地一直是個棘手的健康問題。近來有文章利用電生理技術觀察到,在肌肉釋放的P物質(SP)會抑制酸誘導第三型酸敏性離子通道(ASIC3)所產生的疼痛;而大豆異黃酮的成份之一,genistein,可扭轉SP抑制肌肉酸痛的機制。雖genistein具抗氧化活性和調節免疫的作用,我認為genistein可能透過抑制酪氨酸激酶(PTK),在肌肉傳遞疼痛訊息的機制上扮演不利的角色。本研究發現,先給予genistein會使ASIC3野生型小鼠對酸誘導的痛覺敏感化更劇烈。但先給予genistein並不會使丘腦室旁核(PVA)的神經活性有顯著改變,對腹後丘腦核(VPM)和腹旁丘腦核(VPL)的樹突棘(dendritic spines)也無明顯影響。另外,長期給予genistein可延長酸誘導的痛覺敏感化。為尋找慢性肌肉疼痛的有效療法,我利用酸引起的肌肉疼痛模式,在小鼠體內測試一種自天麻萃取出的腺苷化合物,T1-11。在這項研究中,T1-11和酸性生理鹽水共同注射,可以逆轉genistein增強的疼痛過敏化。而同時注射酸、T1-11和第三型腺苷酸接受器(A3R)拮抗劑MRS1220,可抑制T1-11的作用;表示T1-11可能經由A3R訊息路徑發揮止痛作用。引人注目的是,在疼痛過敏化產生後,腹腔注射T1-11可在90分鐘內看見止痛效果,且藥效與劑量成正比。總結目前研究,先給予genistein會加強酸誘導的疼痛過敏化,而T1-11可經由A3R訊息路徑調節慢性肌肉疼痛達到有效的治療作用。 Chronic muscle pain is often accompanied with tissue acidosis and is an intractable health problem around the world. A recent article indicated that muscular substance P modulated an untraditional NK1 receptor signaling pathway to inhibit the acid-induced depolarization in muscle nociceptors; and genistein, one constituent of soy isoflavones, can reverse this inhibition on muscle nociceptor in vitro. Although genistein has antioxidant activity and beneficial effects on immune system modulation, I hypothesized genistein, as a tyrosine kinase inhibitor, may play a disadvantage role on ASIC3-mediated muscle pain. In the present study, I found that pretreating genistein followed by single acidic saline injection induced mechanical hyperalgesia in WT mice, but not in Asic3 KO mice. ERK activity was no significant changes in the paraventricular thalamic nucleus under genistein-pretreated condition, and dendritic spines in ventral posteromedial thalamic nucleus and ventral posterolateral thalamic nucleus had no changes. Moreover, mice with long-term genistein pretreatment prolonged the effect of acid-induced pain. In search for treatments for chronic muscle pain, I tested the therapeutic effect of a novel adenosine analogue T1-11, purified from Gastrodia elata, on the acid-induced muscle pain model. Co-injection of T1-11 and acidic saline after genistein prevented the chronic hyperalgesia. Coinjecting T1-11 and MRS1220, a selective A3R antagonist, reversed the antinociceptive effect of T1-11, indicating an A3R-dependent signaling involved. Strikingly, after the mechanical hyperalgesia had been developed, intraperitoneal injections of T1-11 can rescue the pain effect dosage-dependently within 90 minutes. Together, the present study indicates that pretreating genistein promotes acid-induced chronic muscle pain, whereas T1-11-A3R signaling inhibits the pain. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65915 |
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顯示於系所單位: | 動物學研究所 |
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