李旺祚2006-07-262018-07-112006-07-262018-07-111999http://ntur.lib.ntu.edu.tw//handle/246246/22835粒線體功能異常會引起許多不同年齡層的神 經病變。最近的研究顯示，抑制興奮性氨基酸的釋 放和施予NMDA 受體的拮抗物，都會減輕粒線體毒 物引起的腦病變。在本計畫中，我們以粒線體呼吸 鏈複合體II 的抑制劑(3-Nitropropionic acid, 3-NP，15mg/kg)為實驗藥物，連續注射於八週大的 Sprague-Dawley 株鼠(n=10)五天，並於第六天以磁 共振影像(MRI)和質譜(1H NMR spectroscopy)來評 估其系列的變化。結果發現Sprague-Dawley 株鼠注 射3-NP 後，會產生紋狀體和海馬迴的病變，並出 現特別的行為變化，這種變化與組織學上的變化一 致。若接受MK-801(2mg/kg) 和Lamotrigine (10mg/kg 和 20mg/kg)的注射，腦病變則明顯改 善，並且行為的變化也消失；磁共振質譜上的變化 則可看到治療後原先NAA 的降低也減輕，並且 Lactate 的昇高也消失。整體而言，在治療的藥物 中lamotrigine(20mg/kg)較lamotrigine(10mg/kg) 和MK-801 能提供更好的保護作用。由於 lamotrigine 的副作用較少，因此更有臨床運用的 價值，值得未來更進一步的研究。Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK- 801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15mg/kg/day) to two-month-old Sprague-Dawley rats (n=10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10mg/kg or 20mg/kg/day) or MK-801 (2mg/kg/day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3- nitropropionic acid injections (P<0.001). The changes were nearly prevented after pretreatment with lamotrigine (20mg/kg). However, the Nacetylaspartate/ creatine in rats pretreated with lamotrigine (10mg/kg) (P<0.01) and MK-801 (P<0.05) still showed significant reduction as compared with sham controls. We conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides better neuroprotective effect than MK-801. With better therapeutic effect and fewer side effects, lamotrigine is more promising for the potential clinical application.application/pdf53872 bytesapplication/pdfzh-TW國立臺灣大學醫學院小兒科NMDA 受體磁共振影像磁共振質譜3-nitropropionic acidT2 mapsmagnetic resonance spectroscopyN-acetylaspartate (NAA)reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/22835/1/882314B002180.pdf