本論文研究目的在於探討大白鼠延腦鼻端網狀腹外側核中細胞訊息傳遞分子 Shc、PYK2、Grb2-sos 複合物、Ras 以及 Raf 蛋白質於美文松中毒過程中所扮演的角色。成熟雄性 Sprague-Dawley 品系之大白鼠 (體重 250-400 克) 作為實驗動物，以腹腔注射 sodium pentobarbital (45 mg/kg) 誘導大白鼠麻醉以便手術之進行。在實驗的全程以持續股靜脈滴注 propofol (20-25 mg/kg/hr) 維持大白鼠麻醉深度之穩定。
微量注射美文松 (10 nmol) 於兩側延腦鼻端網狀腹外側核中，導致動脈壓血管運動成份功率密度 (low frequence, LF) 產生兩期之變化。第一期為動脈壓頻譜之血管運動成份功率高於基準期 (定義為交感神經興奮心血管反應作用)；第二期為動脈壓頻譜之血管運動成份功率低於基準期 (定義為交感神經抑制心血管反應作用)。預先處理 phospho-Shc-tyrosine 317、phospho-PYK2-tyrosine 402、phospho-PYK2-tyrosine 579/580 抗體 (1:20) 或是 Grb2-sos 複合物結合抑制劑 (SH3b-p)、Ras 蛋白質活性抑制劑 (manumycin A 或 FTA) 以及 Raf 蛋白質活性抑制劑 (GW5074) 再給予美文松，皆可發現原本美文松中毒的第一期交感神經興奮心血管反應的功率密度受到抑制，但是美文松作用的時間以及第二期的交感神經抑制心血管反應作用沒有顯著的改變。
綜合本論文之研究結果，我們認為大白鼠延腦鼻端網狀腹外側核中細胞訊息傳遞分子 Shc、PYK2、Grb2-sos 複合物、Ras 以及 Raf 蛋白質參與了大白鼠延腦鼻端網狀腹外側核美文松中毒的交感神經興奮心血管的反應。

We investigated the role of Shc、PYK2、Grb2-sos binding complex、Ras and Raf proteins at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone, in mevinphos (Mev) intoxication. Adult Sprague-Dawley rats anesthetized by sodium pentobarbital (45 mg/kg) and maintained by propofol (20-25 mg/kg/hr) were used.
Bilateral microinjection of Mev (10 nmol) into the RVLM elicited two distinct phases of cardiovascular responses, designated Phase I (sympathoexcitatory) and Phase II (sympathoinhibitory) Mev intoxication. Pretreatment with microinjection of a phospho-Shc-tyrosine 317, phospho-PYK2-tyrosine 402, phospho-PYK2-tyrosine 579/580 antibody (1:20), Grb2-sos complex inhibitor (SH3b-p), Ras specific inhibitors (manumycin A or FTA) or Raf specific inhibitor (GW5074) into the bilateral RVLM blunted the magnitude of the Mev-elicited sympathoexcitatory cardiovascular effect without affecting the duration. The Mev-elicited sympathoinhibitory cardiovascular effect was not influenced.
Our results suggest that signaling pathways that involve Shc, PYK2, Grb2-sos complex, Ras or Raf protein in the RVLM participate in the sympathoexcitatory phase of Mev intoxication.

中文摘要 2 – 4
英文摘要 5 – 6
緒論 7 – 23
研究動機與目的 24 – 25
實驗材料與方法 26 – 30
實驗結果 31 – 37
討論 38 – 52
結論 53 – 54
未來展望 55 – 56
參考文獻 57 – 70
實驗圖表 71 – 115

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