在感染廣東住血線蟲的小鼠乙醯半胱氨酸藉由誘發腦脊髓液嗜酸性白血球凋亡降低腦部傷害

N-acetylcysteine decreases the damage of brain in mice infected with Angiostrongylus cantonensis by induction apoptosis of cerebrospinal fluid eosinophil

陳怡廷(Yi-Ting Chen)

指導教授 ： 顏全敏

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2018年)

摘要

廣東住血線蟲(Angiostrongylus cantonensis)是一種寄宿在嚙齒類動物上的寄生蟲，人類和BALB/c小鼠屬於非適當宿主，生食或未煮熟且受到廣東住血線蟲第三期幼蟲感染的食物便會在非適當宿主體內爬行至腦部發育為第五期幼成蟲(young adult)，並在人類中樞神經系統引起嗜伊紅性腦膜腦炎(Eosinophilic meningitis)，而台灣則屬於廣東住血線蟲感染症的主要流行地區。本研究以BALB/c小鼠為動物模式，區分為未感染組、感染後未治療組與感染後治療組相互比較，藉由未感染組與感染未治療組中相比可知，BALB/c小鼠感染廣東住血線蟲後吸引嗜酸性白血球進入腦部，產生大量活性氧物質(Reactive Oxygen Species, ROS)，形成腦部氧化壓力的傷害。經實驗證實BALB/c小鼠自感染廣東住血線蟲至三十天後，腦脊髓液中細胞因子Interleukin-3 (IL-3)、Interleukin-5 (IL-5) 、 Granulocyte-macrophage colony-stimulating factor(GM-CSF)、活性氧物質和Malondialdehyde(MDA,丙二醛)濃度和量皆顯著增加。乙醯半胱氨酸(N-Acetyl-cysteine, NAC)是一種抗氧化劑也是Glutathione(GSH,穀胱甘肽)的前驅物，具有保護細胞抵禦氧化壓力的傷害。因此，本實驗主要探討BALB/c小鼠感染零至三十天後，感染後未治療組與感染後治療組相比之下，給予BALB/c小鼠乙醯半胱氨酸的治療，有效減少小鼠腦部中活性氧物質和Malondialdehyde濃度或量，同時，促使腦脊髓液中更多的嗜酸性白血球走向程序性細胞凋亡以及提升Glutathione抗氧化物的濃度。由本研究可得知BALB/c小鼠感染廣東住血線蟲後，給予乙醯半胱氨酸可有效降低寄生蟲帶給BALB/c小鼠中樞神經系統各項損傷且由存活曲線統計圖表獲知乙醯半胱氨酸確實明顯提昇BALB/c小鼠感染後的存活率。

關鍵字

廣東住血線蟲 ； 嗜酸性白血球 ； 氧化傷害 ； 乙醯半胱氨酸

並列摘要

Angiostronglus cantonensis, the definitive host is rodents, is one of the most important zoonotic nematodes in Taiwan. The nonpermissive hosts, e.g., humans and mice, are infected via eating the rare or unwell cook food contaminated with the third-stage larvae of A. cantonensis (AcL_3). The ingested AcL_3 will develop to young-adult worms in the central nervous system (CNS) of human and cause eosinophilic meningitis. Mice play an animal model for human, they are infected with A. cantonensis for research. BALB/c mice were divided into the uninfected group, the infected groups treated with N-acetyl-L-cysteine (NAC) and treated with phosphate buffered saline after infection. A. cantonensis infection mainly increases the production of reactive oxygen species (ROS) which cause oxidative stress, and the infection will occur cerebrospinal fluid (CSF) eosinophilia in brain of the infected BABL/c mice. IL-3, IL-5, GM-CSF and Malondialdehyde (MDA) in CSF of untreated infected mice significantly increased at each sacrificed day post-infection compared to the uninfected mice. N-acetyl-L-cysteine is an antioxidant and a precursor of glutathione (GSH), therefore protecting cells from oxidative stress damage. This study aim to estimate ROS production and apoptosis of CSF eosinophils among mice treated with NAC or without treatment after infection with A. cantonensis. Indeed significantly higher concentrations of GSH and apoptosis of CSF eosinophils and significantly lower levels of ROS in CSF and MDA in brain extracts, were observed in mice treated with NAC after infection then that in mice without treatment at each sacrificed day until the 〖30〗^th day after infection. This research confirmed that NAC effectively reduced ROS and promoted CSF eosinophils apoptosis which damaged CNS in infected mice. Thus, significantly increased survivals were observed in BALB/c mice treated with NAC after infection with A. cantonensis compared to mice without treatment with NAC.

並列關鍵字

Angiostrongylus cantonensis ； Eosinophils ； Oxidative stress ； N-acetyl-L-cysteine

參考文獻

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