• 作者： 徐剛; 汪大衛; 沈建業; 江啟輝
• 作者服務機構： 國防醫學院; 三軍總醫院胸腔內科
• 中文摘要： 增加cAMP之藥物對若干種急性肺損傷模型都有良好的保護作用，但是其作用機轉究係透過穩定中介細胞（中性白血球）抑或直接穩定肺泡毛細血管皮細胞，則尚無定論。為了澄清此問題，我們選擇魚精蛋白(Protamine)致肺損傷模型，因其可直接使肺泡毛細血管內皮細胞受損。研究乃採用大白鼠原位離體肺模型；將魚精蛋白(3mg)加入到此模型之無血灌注液中，連續觀察並記錄肺重量以及肺循環灌注壓（肺動脈壓）之變化。然後在給魚精蛋白前分別給予氨苯鹼(6mg)，dibutyryl cyclic AMP (DBcAMP 4mg)及Pentoxifylline (8mg)以觀察保護效果。結果發現魚精蛋白使肺動脈壓明顯增加，由15.6±0.5升至30.8±1.2mmHg (P<0.001)，肺重量與對照組相比亦顯著增加(P<0.001)。預先給以DBcaMP，氨苯鹼和Pentoxifylline對肺動脈壓之增高及肺重量之增加有保護作用，與未頂先給藥而單用魚精蛋白組相比其差異有統計學意義(P<0.05～P<0.001)。至於此保護作用之機轉則認為與增加CAMP有關，因為DBcAMP，氨苯鹼和Pentoxifylline均可增加cAMP，雖然其途徑和機轉不同。由於在灌注液中沒有血液，因此cAMP的保護作用不可能是透過中介細胞（如白血球），而血管內皮細胞可能是重要的靶細胞；因為Protamine是多陽離子藥物，其造成肺損傷的機轉即可能是破壞了血管內皮細胞表面的陰離子層。我們認為此結果對於澄清cAMP對急性肺損傷的保護機轉有重要意義。
• 英文摘要： Polycations, such as protamine sulfate and polylysine, have been implicated in acute lung injury.We studied the vascular effect of protamine sulfate and the protective effect of agents that increase cAMPin isolated rat lungs perfusated with a cell- and plasma-free solution. Protamine sulfate (3 mg) markedlyincreased pulmonary artery pressure (PAP) from 15.6±0.5 to 30.8±1.2 mmHg (P＜0.01)and lung weightgain (LWG) by 7.8±1.5 g within 30 min (P＜0.001). The protective effects of pharmacological agentsthat increase intracellular cAMP were investigated. These agents included dibutyryl adnosiae 3', 5'-cyclicmonophosphate (DBcAMP, a cAMP analogue), aminophylline and pentoxifylline (both are phosphodiesteraseinhilitors). Pretreatmest with these agents 5 min before protamine administration largely atenuated theincreases in PAP and LWG. Because DBcAMP，aminophylline and pentoxifylline all share the effects ofincreasing intracellular CAMP and were effective on the protamine-induced lung changes, the intracellularlevel of cAMP could be a major determinant of lung injury. Since there is no blood in the perfusate, themechanism of cAMP on cellular components in the blood such as neutrophils, can be ruled out. Theendothelial cells are likely to be the target cells because charge interaction is believed to occur on theendothelial surface. This result will be very important in the elucidation of the protective effect of cAMPin acute lung injury.
• 中文關鍵字： protamine; aminophylline; DBcAMP; pentoxifyline; lung injury.
• 英文關鍵字： --