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  • 學位論文

腦缺血與血液再灌流時沙鼠大腦皮質細胞外液中微量元素與能量代謝物質動態變化之研究

Study on the Dynamic Changes of Extracellular Trace Elements and Energy Metabolites in Brain Cortex of Gerbil during Cerebral Ischemia and Reperfusion

指導教授 : 黃友利 劉宏文

摘要


摘要 本研究利用微透析自動採樣技術配合原子吸收光譜儀或微管高效液相層析儀探討腦缺血期間,沙鼠大腦皮質細胞外液中微量元素、能量代謝物或神經傳導物質之動態變化。同時,我們也將探討腦缺血期間,紅血球內鎂、葡萄糖與乳酸濃度之動態變化。我們利用結紮沙鼠右側中腦動脈與右側頸總動脈形成腦缺血狀態。研究結果顯示: 腦缺血期間,鎂濃度明顯降低到腦缺血前的41 % 且於血液再灌流時回升到腦缺血前濃度的67 %。此外,我們也利用雙微透析技術分析兩側大腦皮質細胞外液中鎂與鋅之濃度。研究結果顯示: 腦缺血時,大腦皮質鎂與鋅濃度分別降低到腦缺血前的65 %與74 %。另一方面,我們也分析多巴胺以及它的代謝產物濃度用以探討腦缺血傷害時,銀杏葉萃取物EGb761合併注射免疫抑制劑FK506是否能夠提供協同性之神經保護效果。特別地,多巴胺濃度明顯增加於銀杏葉萃取物EGb761合併免疫抑制劑FK506之組別中。同時,在腦缺血期間,紅血球內鎂濃度大約上升到腦缺血前的130 % 但乳酸降低到腦缺血前濃度的50 %。總之,研究證據顯示: 在腦缺血期間,低濃度的鎂與鋅和高濃度的多巴胺與腦損傷是有密切關係的。除此之外,高濃度的鎂可能有利於紅血球保留葡萄糖並渡過腦缺血危機。

並列摘要


Abstract Microdialysis auto-sampling technique coupled with atomic absorption spectrometry or microbore high-performance liquid chromatography was applied to investigate the dynamic changes of extra-cellular trace elements, energy metabolites, or neurotransmitter in brain cortex of gerbil during cerebral ischemia. Meanwhile, dynamic changes of the concentration of magnesium, glucose, and lactate in erythrocytes during cerebral ischemia will be explored. Cerebral ischemia was induced in gerbil by occlusion right middle cerebral artery and right common carotid artery. Our finding indicated that level of magnesium was significantly decreased to 41 % of the baseline during ischemia and returned to 67 % of the baseline after reperfusion. In addition, dual-probes microdialysis technique was used to analyze the level of extra-cellular magnesium and zinc in both sides of the cortex. Results showed that a significant decrease in magnesium (65 % of baseline) and zinc (74 % of baseline) was seen on the ischemic side of cortex during ischemia. On the other hand, concentrations of dopamine and its metabolites were also determined in the present study to investigated whether EGb761 coadminister with FK506 could provide a synergistic effect on neuro-protection during ischemic damage. Specifically, a remarkable elevation of the dopamine level was seen in the group of EGb761 plus FK506. Meanwhile, an approximately 130 % of the baseline level of magnesium and 50% of the baseline level of lactate were seen in the erythrocyte during cerebral ischemia. In summary, evidences suggested here that during cerebral ischemia, lower magnesium, zinc and higher dopamine level may be associated with the damage of brain. In addition to this, higher magnesium level may be advantageous for erythrocytes in preservation the glucose level and overcoming the crisis of cerebral ischemia.

參考文獻


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