高體熱引發鼠肝損傷發病機轉中一氧化氮角色之探討

The Role of Nitric Oxide Involved in the Liver Injury Induced by Hyperthermia in Rats

暴露在熱環境中可使人由不舒適到臟器器官受損甚至危害到生命。體內溫度過高如熱中暑會造成全身組織系統的損傷，如心臟、肝臟、急性呼吸窘迫症候群及瀰漫性血管內凝血病變等合併症，但發病機轉仍然不完全明暸。本研究利用清醒大白鼠模式，探討在熱壓力下，在42°C熱水浴中停留一小時後之肝功能損傷情形，並分析血中氧游離基及一氧化氮含量之變化；肝組織則進行免疫螢光染色以觀察硝基酪胺酸(nitrotyrosine)之表現，以探討氧化壓力及氮化壓力在肝功能損傷中扮演之角色。實驗結果證實42°C熱水浴1小時所產生的熱壓力在14小時後使老鼠肝功能指數AST、ALT(p<.05)及LDH(p<.001)明顯上升，血中氧游離基及一氧化氮濃度增加(p<.05)；免疫螢光染色結果也證實硝基酪胺酸呈明顯地之表現。此結果說明肝臟在熱壓力刺激後，氧游離基代謝產物會增加，血中一氧化氮含量會上揚，其中一氧化氮與氧游離基之代謝產物如過氧亞硝酸(peroxynitrite)，以及其它相關之游離基可能是造成肝損傷之主要原因。The effects of excessive heat accumulating in the body are life threatening. Clinical and laboratory findings demonstrated that it is a form of hyperthermia-associated organ injuries. However, the mechanisms involved still remain unclear. In this study, the Sprague-Dawley rats were exposed to hyperthermia by immersing the conscious rats into water bath and heated the water to 42°C and remained for one hour. Whole blood samples were taken before hyperthermia and 14 hrs after heat challenge and blood concentrations of AST, ALT, LDH, oxygen radical and nitric oxide were measured. After experiments, liver tissues were taken for analysis of the protein expression of nitrotyrosine by immunohistochemistry analysis. The results showed that Blood levels of AST, ALT, LDH, oxygen radical and nitric oxide increased significantly. The protein expression of nitrotyrosine increased also significantly. The researcher concluded that hyperthermia could induce liver injury and the production of oxygen radicals, nitric oxide and the increase of their reaction products, peroxynitrite and other related radicals, may play the critical roles in the hyperthermia-induced liver injury.