ASIC3和TRPV1基因缺乏小鼠在異丙腎上腺素造成心肌缺血後的基因表達

Gene expression patterns in ASIC3 and TRPV1 deficient mice after isoproterenol-induced myocardial ischemia

許若姍(Jo-shan Hsu)

指導教授 ： 孫維欣

國立中央大學/理學院/生命科學系/碩士(2014年)

摘要

胸痛是心肌缺血的標誌，時常發生於心臟時沒有獲取足夠的氧氣時。心肌缺血會引起氫離子 (proton)或緩激肽 (bradykinin)的產生，激活心臟初級傳入纖維，特別由Aδ和C纖維傳入，轉導心臟痛覺至中樞神經系統，從而導致疼痛。在前人研究中指出第三型酸敏感離子通道 (ASIC3)在傳遞心臟感覺的神經束上，可能參與在心肌缺血後的調控，在前人實驗中ASIC3-/-小鼠短暫的心肌缺血時，會使心電圖引起長時間的ST段壓低和心肌纖維化，但不會在ASIC3 +/+小鼠或TRPV1-/-小鼠中發現此作用。然而，分子參與缺血誘導的疼痛是目前還並不明確。
因此在這項研究中，我利用小劑量異丙腎上腺素 (isoproterenol)誘導ASIC3或TRPV1基因剔除的小鼠短暫性心肌缺血，異丙腎上腺素注射後在心臟肌肉會造成短暫的缺氧。在異丙腎上腺素注射後氫離子敏感的G蛋白偶合受體(proton-sensing GPCR)的G2A基因表現增加。在ASIC3基因缺乏小鼠會提早發生心肌缺氧反應，而G2A基因表現量會受到抑制。因此G2A基因可能參與ASIC3調控的途徑，保護心肌細胞以避免受到缺血性造成的損傷。

關鍵字

心肌缺血 ； 異丙腎上腺素 ； 第三型酸敏感離子通道 ； 辣椒素受體

並列摘要

Chest pain is the hallmark of myocardial ischemia, that often occurs in heart when sufficient oxygen for the needs is not acquired. Myocardial ischemia induces production of proton or bradykinin, which activates cardiac primary afferents, specifically Aδ- and C-fibre afferents, to transduce cardiac nociception to the central nervous system, leading to pain. In previous studies, acid-sensing ion channel 3 (ASIC3) on cardiac sensory afferents to sense protons and some regulations, participate in the regulation of myocardial ischemia. Transient myocardial ischemia induces prolonged ST-segment depression and more severe cardiac fibrosis in ASIC3-/-, but not in ASIC3+/+ or TRPV1-/-. However, molecular involved in ischemia-induced pain is not clear.
In this study, I used low-dose isoproterenol to induce transient myocardial ischemia in ASIC3 or TRPV1 knockout mice. Isoproterenol injection caused transient hypoxia in cardiac muscle. Expression of proton-sensing G-Proton-coupled receptor(GPCR) G2A,was increased after isoproterenol injection. In ASIC3-/- mice, transient hypoxia occurred early and G2A expression was inhibited.
Therefore, G2A may participate in ASIC3-mediated pathway to protect cardiac cells from severe ischemic insults.

並列關鍵字

Ischemia ； Isoproterenol ； ASIC3 ； TRPV1

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