甲苯達唑及槲皮素對鼷鼠廣東血線蟲症炎症反應之影響

Effects of Mebendazole and Quercetin on Inflammatory Responses in Murine Angiostrongyliasis

廖育正(Yu-Chen Liao)

指導教授 ： 蘇霩靄

國立臺灣大學/醫學院/微生物學研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.00727

摘要

廣東血線蟲是台灣和東南亞地區嗜酸性腦膜腦炎的主要病因。有學說指出，若寄生腦內的幼成蟲被藥物迅速殺害，死去的蟲體可能在宿主腦內引發嚴重的發炎反應並造成神經損傷。因此，至今在臨床治療上通常都不建議採用驅蟲藥物。此外，用以緩和宿主腦內發炎反應的類固醇藥物是否具有功效，也是個具有爭議性的問題。本研究主要是在探討甲苯達唑的治療效力及其對宿主免疫反應之影響。近年來相當受關注的類黃酮抗發炎藥物—槲皮素之抑制發炎功效，也是探討的重點之一。BALB/c鼷鼠在口服感染30隻感染型幼蟲後，分組進行實驗—不投予任何藥物、僅投予甲苯達唑、或合併投予甲苯達唑及槲皮素。另外，我們以未受感染的正常鼷鼠作為控制組。本研究利用酵素連結免疫吸附法（enzyme-linked immunosorbent assay）測定宿主腦脊髓液及周邊血液中細胞激素的濃度；亦透過鏡檢技術觀察宿主腦脊髓液中嗜酸性白血球之比例及廣東血線蟲幼成蟲之回收數目。此外，亦利用反轉錄聚合酶鏈鎖反應（reverse transcriptase-polymerase chain reaction）技術偵測宿主腦內細胞激素之訊息核醣核酸（messenger RNA）表現情形。本研究結果顯示，接受適當甲苯達唑治療之感染組鼷鼠，其腦內蟲體回收率約降低80-95%；其IL-4及eotaxin這兩個和造成宿主嗜酸性白血球浸潤相關之細胞激素的表現，也明顯地較未治療者低；此外，其腦內嗜酸性白血球之比例亦顯著下降。儘管在感染前期或後期甲苯達唑合併槲皮素治療的方式都能夠降低宿主腦內IL-4和eotaxin的表現量，但其效果並不如預期。本研究更意外地發現IL-5的表現量相當地低，在宿主被感染後三週其表現更是低至無法偵測的程度。本研究的結果顯示，使用驅蟲藥物治療此病或許不會引發如前人假說中所警告之嚴重後果。此外，IL-5於此病病程中所扮演的角色，或許亦不如預期中重要。

關鍵字

廣東血線蟲症 ； 甲苯達唑 ； 槲皮素 ； 嗜酸性腦膜腦炎 ； 細胞激素

並列摘要

Angiostrongylus cantonensis is the major cause of eosinophilic meningoencephalitis in Taiwan and Southeast Asia. Clinically, anthelmintic treatment is usually not recommended due to concerns about the theoretical neurologic side-effects caused by degenerating worms. In addition, the efficacy of steroid therapy is also controversial. In the present study, the efficacy of mebendazole treatment was examined. Effects of mebendazole treatment on host immune responses were also investigated. In addition, the anti-inflammatory efficacy of quercetin, a popular flavonoid antiphlogistic, was also evaluated. BALB/c mice were infected with 30 infective larvae per os and underwent different therapeutic strategies—without any drug treatment, treated with mebendazole only, or treated with mebendazole and quercetin. Non-infected mice served as negative controls. Cytokine concentrations in cerebrospinal fluid and peripheral blood were determined through enzyme-linked immunosorbent assay. Eosinophil counts in CSF as well as worm recovery in brains were also determined under the microscope. Cytokine mRNA expressions in mouse brains were also investigated using reverse transcriptase-polymerase chain reaction assay. The results of this study revealed that, with proper timing and dosages of mebendazole treatment, worm recovery rates were reduced about 80-95 %. The data also showed that instead of raising the expression of IL-4 and eotaxin, which are CSF eosinophilia-related cytokines, mebendazole medication suppressed the expression levels of these cytokines both in protein level and in mRNA level. Eosinophil counts in CSF were also significantly lowered in the treated mice. Concomitant administration of mebendazole and quercetin to infected mice did suppress IL-4 and eotaxin production in CSF both in the early and late onset of treatment groups, but the efficacy was not so remarkable as we expected. Interestingly, IL-5 expression was only detected in a very low level at 14 days post-infection and even undetectable at 21 days post-infection. These data suggested that anthelmintic treatment to angiostrongyliasis patients might not be as harmful as generally expected. Furthermore, IL-5 might not be the major factor in the course of this disease.

並列關鍵字

angiostrongyliasis ； mebendazole ； quercetin ； eosinophilic meningoencephalitis ； cytokine

參考文獻

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