雙酚化合物在文獻報導中發現具有抗發炎和抗氧化的能力，因為其親脂性的特性，雙酚化合物可以輕易穿透血腦屏障到中樞神經系統發揮其藥理活性。因此，雙酚化合物被評估可做為潛在預防及治療神經退化性疾病如帕金森氏症的神經保護藥物。本研究目的為探討新合成的雙酚化合物MH101及MH102是否具有神經保護和治療效用，而對抗神經毒素(包含巴拉圭、過氧化氫及MPTP)引起的神經毒害及其誘發的動物行為異常(如: 學習、記憶及運動協調)。研究中應用Oregon-R的果蠅(年齡: 1-2, 7, 20 和 30天)做為檢測模式，果蠅暴露在巴拉圭 (5-20 mM)或過氧化氫(0.3 %-3 %)環境下，並且給予MH101 (0.1-3 μM)。結果顯示MH101未能有效地減緩巴拉圭及過氧化氫所引起果蠅壽命的下降。此外，給予雄性ICR小鼠 (25-30 g) 腹腔注射MPTP (25mg/kg)每天一次連續五天，觀察神經毒素誘發的行為異常和神經毒害。在觀察保護效果的研究中，雄性小鼠在給予MPTP前一小時腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg) 每天一次連續五天，之後單獨給予MH101或MH102治療連續九天。後處理的組別，雄性小鼠在給予MPTP每天一次連續五天後，每天腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg)連續九天。控制組組別，小鼠則給予生理食鹽水(0.9%)及玉米油的混合液。結果顯示，MH101、MH102及MPTP皆不影響小鼠橫桿行走試驗的運動平衡和協調能力。然而，在前處理和後處理MH101或MH102後用新位置辨識能力測試和新物體辨識能力測試觀察MPTP引起的認知缺失，實驗結果顯示MH101及MH102皆恢復短期記憶和長期記憶的認知辨識指標。另外，前處理和後處理MH101或MH102雖有些微恢復紋狀體內MPTP引起多巴胺神經損傷及多巴胺轉運子減少的趨勢，但不顯著。由此推論，雙酚化合物MH101及MH102具有預防及改善神經毒素所引發的認知與學習缺陷，未來可能發展成為神經退化性疾病如帕金森氏症之潛力治療藥物，另針對MH101及MH102在神經損傷及動物行為障礙的恢復和保護藥理機制則需進一步實驗探討。 / Biphenols which are the main constituents of the traditional herbs have been found to possess the antiinflammatory and antioxidative properties. Due to the lipophilic activity, biphenols can readily cross the blood brain barrier to exert their pharmacological effects in the central nervous system. Thus, biphenols are proposed to act as the novel neuroprotective agents for treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether the new synthetic biphenolic compounds MH101 and MH102 have the neuroprotective and therapeutic actions against the neurotoxicity and the behavioral impairments (e.g. learning, memory, and motor coordination) induced by neurotoxins including paraquat, hydrogen peroxide, and MPTP in PD-like animal models. The following experiments examined the lifespan of flies from Oregon-R strain of Drosophoila melanogaster (age: 1-2, 7, 20 and 30 days) chronically exposed to paraquat (5-20 mM) or hydrogen peroxide (0.3 %-3 %) under MH101 (0.1-3 μM) treatment. Our results showed that MH101 could not effectively influence the reduced lifespan of the flies induced by paraquat and hydrogen peroxide. Furthermore, male ICR mice (25-30 g) were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neuronal damage and cognitive deficits. For the protective study, male mice were administrated with MH101 (1-3 mg/kg, i.p.) or MH102 (0.1-3 mg/kg, i.p.) 1 hour prior to MPTP injection once daily for 5 days, and followed daily treatment with MH101 or MH102 alone for consecutive 9 days after the final injection of MPTP. For the post-treatment study, male mice were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days, and followed by daily treatment of MH101 or MH102 for 9 days. Mice in control group were injected with vehicle (0.9% saline + corn oil). The results showed that MH101, MH102, and MPTP alone did not alter the motor functions of coordination and balance in beam walking test. On the other hand, both pre-treatment and post-treatment of MH101 and MH102 reversed the cognitive dysfunction induced by MPTP detected by novel location recognition test (NLRT) and novel object recognition test (NORT). Data demonstrated that MH101 and MH102 reversed the reduction in recognition index (RI) of short term memory and long term memory in MPTP-induced PD model. However, pre-treatment and post-treatment of MH101 or MH102 slightly recovered MPTP-induced loss of dopamine neurons and dopamine transporter in striatum. Therefore, the results suggest that biphenols including MH101 and MH102 may be the candidates for treatment of neurodegenerative diseases such as PD. In the future, it will need further study to determine the pharmacological mechanism of MH101 and MH102 in protection and restoration of neuronal injury and cognitive impairment.

近年來，國際體系已從冷戰期間的兩元化趨向為現今的多元化發展，國際關係中國家角色的定位亦已由消極地孤立、不結盟朝向結盟、區域整合與全球化的目標邁進，並積極地參與國際政治與經濟組織，以因應全球競爭白熱化的趨勢。有鑑於此，全球性及區域性的經貿組織如雨後春筍般盛行，為當今國際經濟與金融新秩序之整合，注入一股欣欣向榮的氣象。 　　巴拉圭向為堅決反共的國家，在東西冷戰結束後邁向民主政治，並於國際上力求擺脫從前孤立形象，重返國際舞台，在其所參與之許多國際組織中，尤以當今第三大經貿集團─南錐共同市場，對其國家發展影響至深且鉅。巴拉圭在南錐共同市場四個創始會員國中雖屈居弱勢，但其如何能在南錐強鄰間運用外交政策─折衝、斡旋，並以四兩撥千金方式，強化本身競爭利基，積極謀求開創新的國家角色，實為巴拉圭未來在南錐共同市場發展所需面臨的挑戰與深思的課題。再者，當整合階段若仍處於較低階的國家層次時，遇國家利益與區域利益相衝突，各會員國往往以國家利益為先。因此，在南錐共同市場的整合過程中與各會員國間互動關係、定位、「區域角色」的扮演、以至於如何達成高層次的區域調和，循序漸進地朝向經濟整合程序邁進，著實對巴拉圭與其他會員國的政治與經濟皆產生莫大之衝擊，巴拉圭政府如何在國家利益與區域利益中取得平衡點並採取有效的因應策略，亦是其國家發展中需面對的另一重大考驗。 　　本論文共分為七章。第壹章緒論，第貳章闡述國際關係中角色理論之基本概念、層次分析及類別，強調在詭譎多變的國際關係中，國家仍一貫扮演最重要的角色，第參章從歷史發展軌跡中探討巴拉圭的國家角色及其外交政策取向之演變，尤其對巴拉圭與巴西及阿根廷之雙邊與三邊互動關係，做一全盤性的概述，以便增進對巴拉圭所處之整體情勢有所了解。第肆章主要針對巴拉圭加入南錐共同市場之政治與經濟動機，和不同面向之內、外在環境時空背景作剖析，第伍章說明南錐共同市場靜態面的基本制度、原則、組織架構與功能介紹及動態面的整合運作模式；以析論南錐共同市場區域內整合深化程度與區域外廣化之關係。第陸章探討巴拉圭在南錐共同市場之角色定位，藉由其發表之「南錐共同市場政策白皮書」檢視其外交政策，並對其在南錐共同市場之未來運作趨勢與影響作深入研究，第陸章結論，就巴拉圭之國家角色和區域角色之互動機制作一總結，旨在對巴拉圭加入南錐共同市場之前景與挑戰賦予嶄新的期許，期能透過政治對話、經濟同盟，創造競爭優勢。第柒章為結論。 / The purpose of this thesis is twofold. The first is to describe and obtain some stylized facts about Paraguay's insertion into MERCOSUR and clarify how this trading bloc enables the economic integration among its members. The second is to analyze the likely economic policies that Paraguay, a small country, may develop in order to identify her own available options, bearing in mind her landlocked but geo-strategic position in the Common Market. The scope on Paraguay's vocation for the democracy consolidation, as well as her pursuit to take due advantages of her abundant hydroelectric energy, and to become into a logistic production and services center for those who are interested in exploring the huge market of more than 200 millions consumers of MERCOSUR, also takes place in this paper. Since the creation of MERCOSUR, Paraguay had to face, frequently, outward difficulties in its efforts to remove non-tariff barriers imposed mainly by its two big neighbours - Brazil and Argentine, beside inward political disagreement and impasse. Her traditional open and informal market precises the due governmental and economical reforms, so her private sector may stands still in the present stage of a consolidating and challenging custom union. The gradual decline of Paraguay's Eastern City - Ciudad del Este, as a prototype of the commerce of re-exportation shows a clear sign of alert to the whole subsisted economy system, that may not apply for the forthcoming trend of mayor competitiveness, since its incompatible pattern with the new scheme of integration, must find its own way to harmonize Paraguay's and MERCOSUR'S joint interests. That means there is still a lot of reforms to be done. For the application of mid and long term trade policies, the year 2006 - time when full-fledged liberalization under IMERCOSUR will become a reality, may appear much closer for Paraguay. At that time, there won't be any exception more for Paraguayan products in MERCOSUR, and it's a must, for the sake of Paraguay, that the domestic debate of reforms concludes into successful process with no more delay nor hesitation. In this respect there are grounds for certain optimism as we can notice in the maquila sector, since some public and private sector have shown its determination to change the stagnant statu-quo, and to adapt the due framework to the needs of a better tomorrow. This work carefully documents the English translation of the agreement that gave life to MERCOSUR, also known as the Asuncion Treaty, in honor of the Paraguay's capital city where the historical and political decision took place.