https://scholars.lib.ntu.edu.tw/handle/123456789/197913
標題: | 氧化氮在MPTP神經毒理作用中所扮演的角色 | 作者: | �d��� | 關鍵字: | MPTP;nitric oxide;Parkinsonism;7-nitroindazole;L-NG nitro arginine methyl ester;microdialysis | 公開日期: | 1999 | 出版社: | 臺北市:國立臺灣大學醫學院神經科 | 摘要: | Methyl-4-phenyl- 1,2,3 ,6-tetrahydropyridine (MPTP) is known to produce parkinsonism in humans and monkeys. Our previous studies have shown that MPP induced dopamine depletion and hydroxyl radicals formation and lipid peroxidation in the striatum of rats. Recent reports have suggestec. that MPTP toxicity could be prevented by 7-nitroindazole (7-NI, a potent inhibitors of neuronal nitric oxide synthase). It is suggested that MPP may interfere with mitochondrial electron transport and result in a leakage of superoxide anion. Nitric oxide (N0), produced following activation of N-methyl-D-aspartate (NM JA) receptors, combined with superoxide to form the toxic free radical peroxynitrito, which in turn may degenerate into more noxious hydroxyl radical and cause cell damage. However, evidence suggested that another nitric oxide synthase (NOS) inhibitor, L-N¢X nitro arginine methyl ester (L-NAME, another NOS inhibitor) did not show protection against MPTP-induced toxicity in the marmoset. Using the IvIPTP-Parkinsonism model, the present study showed that both of 7-NI and L-NAME did not exert protective on dopaminergic neurons in term of the inhibition of dcpamine depletion and hydroxyl radical formation induced by MPP in the striatum. 已知1-methy-4-phenyl-1 , 2 , 3 , 6 -tetrahyd ropylidine ( MPTP )是一種特殊的神經毒素,能夠在人類及靈長類誘發酷似巴金森氏病(巴病)的病理及臨床變化。過去我們已證明MPP +能夠在大鼠的紋伏體造成巴多臏之異常釋放dopamine depletion ) ,產生經基自由基及脂質過氧化物。最近有報告指出一種氧化氮合成酵素抑制劑7 - nitroindazol ( 7 -Nl )能夠預防MPTP 之毒性。 PTP 的毒性代謝產物MPP + 能夠干擾粒腺體電子傳遞系統,產生自由基superoxide anion 經由活化N – methyl-D-aspartate ( NMDA )接受體而產生的NO能夠與superoxide 結合形成自由基peroxynitrite ; peroxynitrite 進一步分解形成QH 自由泳而對細胞產生傷害。然而亦有研究發現另一種NOS 抑制劑L-NG nitro arginine methy l- ester ( L-NAME )卻無法在一種中南美洲小;袁猴(marmoset )身上對抗MPTP 之毒性。本研究利用顱內微透析法進一步探討NOS 抑制劑,包括7-Nl 及L-NAME 對MPP+在紋狀體內所誘發的多巴銨之過度溢流,多巴膠的代謝產物及形成經基自由基一祖影響,結果發現兩種藥物都無法保護神經細胞對抗MPP+之毒性。 |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/26074 | 其他識別: | 882314B002288 | Rights: | 國立臺灣大學醫學院神經科 |
顯示於: | 醫學系 |
檔案 | 描述 | 大小 | 格式 | |
---|---|---|---|---|
882314B002288.pdf | 221.16 kB | Adobe PDF | 檢視/開啟 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。