| 摘要: | 廣東住血線蟲感染症是盛行於台灣、大陸東南沿海地區及泰國、柬埔寨等東南亞國家的人畜共通寄生蟲病，並由感染廣東住血線蟲 (Angiostrongylus cantonensis) 所引起。在人類及小鼠等非適當宿主中，幼蟲在入侵非適當宿主腦部後便會死亡，死亡的幼蟲會造成嚴重的腦部發炎反應，引起噁心、嘔吐、發燒、視覺障礙等症狀，更會因引起嗜酸性腦膜炎使非適當宿主死亡。目前對於廣東住血線蟲感染症腦部發炎及其相關免疫病理致病機轉仍不清楚。本研究以SD大鼠作為適當宿主及以ICR小鼠作為非適當宿主的實驗動物模式，利用核醫影像系統18F-FDG-PET活體動物影像評估模式，偵測廣東住血線蟲感染症所引起的腦部發炎程度並以分子生物學實驗分析腦部發炎相關因子之基因及蛋白表現，藉以探討腦部發炎因子與核醫影像數值的關聯性。核醫影像結果顯示，感染的大鼠腦部的18F-FDG累積在額葉皮層等周邊組織中並在感染4週後有顯著上升；相較於感染的大鼠，感染的小鼠腦部18F-FDG累積區域主要為杏仁核、紋狀體、額葉皮質及視丘，其累積量隨著小鼠感染週數增加而上升。在組織病理研究結果中，感染的小鼠腦部在感染2週後發現開始有小膠質細胞與嗜酸性球聚集，於感染4週後出現大量小膠質細胞聚集及嗜酸性球浸潤；在感染的大鼠腦部則沒有觀察到上述的病理變化。在腦部發炎因子基因及蛋白表現分析中，小鼠腦部Ym-1、c-Fos的表現量隨著感染週數增加而逐漸上升，Iba-1則是在感染第2週大量增加後於4週下降；相關腦部發炎因子基因及蛋白表現在感染的大鼠腦部則沒有顯著差異。而將18F-FDG-PET數值與蛋白質表現進行相關分析之後發現，Ym-1與IL-4隨著感染時間變化，PET的數值與蛋白質的表現趨勢呈現正相關。本研究證明可以利用18F-FDG-PET活體動物影像評估模式來檢測廣東住血線蟲感染症宿主腦部發炎病理損傷的變化，並有助於未來建立更精確的18F-FDG-PET成像評估模型，除可用於分析廣東住血線蟲等人畜共通寄生蟲感染所引起的腦部免疫病理機轉外，未來可應用於由病原體感染所引起的腦部發炎臨床病理診斷。
The Angiostrongylus cantonensis infection is a common parasitic disease common to humans and animals in Taiwan, southeast coastal areas of China and Thailand, Cambodia and other Southeast Asian countries, it caused by infection with Angiostrongylus cantonensis. In an definitive host, the larvae will enter the lungs and mature into adult worms after passing through the rat brain; in paratenic host such as humans and mice, the larvae will die after invading the brain, and the dead larvae will causes severe brain inflammation, causing symptoms such as nausea, vomiting, fever and visual impairment, it even causes death of paratenic host due to eosinophilic meningitis. At present, it is still unclear as to the brain inflammation and related immunopathological pathogenesis of Angiostrongylus cantonensis infection. This study uses SD rats as the definitive host and ICR mice as the paratenic host, using the nuclear medicine imaging system 18F-FDG-PET live animal image assessment mode to detect the degree of brain inflammation caused by Angiostrongylus cantonensis infection, and using Molecular biology experiment to analysis of gene and protein expression of brain inflammation-related factors to explore the correlation between brain inflammation factors and nuclear medicine imaging. Nuclear imaging results showed that 18F-FDG in the brain of infected rats accumulated in the Cortex Frontal and Cortex Medial, Olfactory and other peripheral tissues and increased significantly after four weeks of infection; compared with infected rats, infected mice the accumulation area of 18F-FDG in the brain is mainly Amygdala, Striatum, and Thalamus, and its accumulation increases with the number of weeks of infection in mice. In the results of histopathological studies, the brains of infected mice were found to have aggregated microglia and eosinophils two weeks after infection, and a large number of microglia aggregation and eosinophil infiltration appeared four weeks after infection. The above-mentioned pathological changes were not observed in the rat brain. In the analysis of brain inflammatory factor gene and protein expression, the expression of Ym-1 and c-Fos in the mouse brain gradually increased with the increase in the number of weeks of infection, and Iba-1 was in the second week of infection after a large increase, it gradually decreases with the increase in the number of weeks of infection; Related brain inflammatory factor genes and proteins showed no significant difference in infected rat brains. By analyzing the correlation between 18F-FDG-PET value and protein expression, we found that Ym-1 and IL-4 were positively correlated with infection time, PET, and protein value trends. This study proves that the 18F-FDG-PET live animal image evaluation mode can be used to detect changes in the pathological damage of the brain of the host of Angiostrongylus cantonensis infection, and it will help to establish a more accurate 18F-FDG-PET imaging evaluation model in the future. It can be used to analyze the brain immunopathology mechanism caused by the common parasitic infection of human and animal such as Angiostrongylus cantonensis, and it can also be used in the clinical pathological diagnosis of brain inflammation caused by pathogen infection in the future. |
