王朝鐘, 李秀雄Wang Chau-jong, Lee Hsiu-hsiung歐嘉仁Ou, Chia-jenChia-jenOu醫學研究所2026-10-289999-12-31https://handle.ncl.edu.tw/11296/yyz42fhttps://scholars.csmu.edu.tw/handle/123456789/34945為探討廣東住血線蟲所引起的致病機轉, 便以三種驅蟲藥如 milbemycin D, VD-99-11及albendazol治療感染廣東住血線蟲第三期幼蟲 小鼠, 於感染後第5, 25及42天解剖,取宿主腦部組織萃取液, 以生化電泳 分析(SDS-PAGE), 西方墨點分析法(western-blot)分析腦內是否有特異性 蛋白出現以偵測其protein kinase C(PKC), ferritin及原致癌基因c- jun, c-fos與c-myc蛋白表現量是否與對照組有差異, 以作為與傳統治療 效果評估之比較, 同時藉由實驗所得的結果來探討廣東住血線蟲對宿主的 致病機轉.實驗結果在感染廣東住血線蟲而未加以治療, 以及VD-99-11治 療之小鼠腦部組織細胞核部分的萃取液之SDS-PAGE電泳分析中發現有一分 子量約為50-kDa的蛋白表現, 然而在未與感染及以milbemycin D, albendazole治療組之小鼠腦部組織中卻沒有此特異性的蛋白質出現; 據 此, 我們認為以生化方法初步評估治療效果是可行的; 在進一步的實驗中 我們發現PKC, ferritin與c-jun,c-fos, c-myc蛋白測定可得到在實驗組 中的未治療組與未治癒組與陰性對照組比較, 亦有亦有顯著的差異; 可發 現PKC在感染初期(第5天), 在感染組皆有明顯大量表現PKC; 在感染各組 與陰性對照組的PKC表現量相當; 在感染第42天, 感染組的PKC表現量明顯 小於陰性對照組, 然而, ferritin, c-jun, c-fos與c-myc在陽性對照組 與VD-99-11治療組的蛋白表現量都隨感染時間的延長成正比增加其表現 量. 依據以上的實驗結果, 我們大概可了解廣東住血線蟲之致病原因可能 和PKC translation, ferritin的表現及致癌基因c-jun, c-fos與c-myc蛋 白活化之間的相關性, 唯其詳細機轉有待進一步探討.In this studies, we have investigated the pathogenesis of the Angiostrongylus cantonensis. The objectives of this work are to compare the effects of three kinds of the drugs as milbemycin D, albendazole and VD-99-11, besides this, I proposed to study the effect of the parasite in ICR mice, in vivo model and evaluate the traditional and biochemical chemotherapeutics. We have taken some laboratory techniques like sodium dodecyl sulfate- polyacrylamide gel electro-phoresis(SDS-PAGE), western-blot, to analyze the extracts of the brain tissue. In order to check the different changes of protein, including some distinguishing protein, ferritin, protein kinase C(PKC) and three kinds of protooncogenes(c-jun, c-fos and c-myc). Several clinical diagnostic criteria have been applied to evaluate the clinicalmanifestation as well as the underlying mechanism for the parasite disease(angiostrongyliasis) development, including the hematological, pathological, biochemicaland molecular biological examinations of the infected mice at different time periods of infections. The results of this experiment: significantly increased inboth leukocyte and eosinophil counts have been found among the infected mice thanthose of controls. Evident inflammatory,infiltrative tissue as well as otherpathologic changes were noticed by histolog-ical examinations of the infected andincured mice. In addition, we have found the 50-kDa protein band pattern was quantitatively increase in brain nucleus from the Angiostronglus cantonensis infected and incuredmice, however, it was almost absent in normal and cured mice. And another proteinvariation, ferritin, was also been found in the nucleus of brain. Besides these, obvious express-ions of both cytoplasmic and membranous PKCs were detected by western blotting analysis. In the other hand, the results of western-blot have been demonstrated that increased, significant expressions of c-jun, c-fos and c-myc. Although this studyhas provided some evidences to elucidate the causal relationship between Angiostrongylus cantonensis infection and pathogenesis, however, the underlying mech-anism still needs to further clarified.驅蟲藥廣東住血線蟲鐵蛋白蛋白激原致癌基因milbemycin DalbendazoleVD-99-11Angiostrongylus cantonensisferritinprotein kinase Cthesis