- 學位論文
在老鼠體內Curcumin對LPS靜注及盲腸結紮穿孔手術所誘發凝血病徵的保護性效果
The Protective effects of Curcumin on Coagulopathy induced by LPS infusion & CLP in Rats
摘要
薑黃素，是薑黃的主要成份之一，其具有減少NF-кB轉錄因子的表現，以及各種發炎因子與cell surface adhesion molecules的數量。瀰漫性血管內凝血(disseminated intravascular coagulation)為一種後天性的症候群，其特性在於全身的血管形成microthrombi 和 fibrin deposition，且通常伴隨有複雜的出血傾向及器官衰竭。而此實驗的目的，在於利用實驗動物探討薑黃素是否在瀰漫性血管內凝血中，具有其保護性效果。在實驗室，利用lipopolysaccharide (LPS)每公斤體重10mg的劑量，經由尾靜脈以4小時持續性注射的方式；以及盲腸結紮穿孔手術(cecal ligation and puncture)--其為一廣泛接受的腹腔內敗血症動物模式，用以引發大白鼠瀰漫性血管內凝血。在結果顯示，大白鼠經過curcumin前處理後，可以保護大白鼠在LPS的處理下預防(1)末稍血液中血小板數目下降，(2)血漿中fibrinogen的數量消耗，(3)減少血循中TNF-α在血漿中的濃度，(4) 降低纖維栓子沉積於腎絲球內。在CLP模式中，薑黃素在6小時的時間點時，可抑制血小板的下降，但卻依然無法減低fibrinogen的下滑。此結果顯示，薑黃素在endotoxemia 或嚴重感染中所表現的coagulative-inflammatory cascade 中顯示出其治療的可能性。因此我們建議在感染時，curcumin的使用助於預防瀰漫性血管內凝血的發生。
並列摘要
Curcumin, a diferuloylmethane derived from turmeric (Curcuma longa), has been shown to down-regulate transcription factors NF-кB and to suppress of various inflammatory mediators and cell surface adhesion molecules.Disseminated intravascular coagulation (DIC) is an acquired coagulopathy characterized by systemic formation of microthrombi and fibrin deposition in the vasculature and often complicates with bleeding tendency and organ dysfunction .The study was designed to investigate the protective effect of curcumin against DIC.Experimental DIC was induced by sustained infusion of 10mg/kg lipopolysaccharide (LPS) for 4hrs via rat tail vein and by Cecal ligation and puncture (CLP) animal model,a well-accepted animal model of intra-abdominal sepsis.Curcumin was given 60mg/kg by intraperitoneal injection .It was found treatment by curcumin could prevent (1) the decrease of peripheral platelets (2) the fibrinogen consumption (3) decrease the circulating TNF-α concentration and (4) decrease the fibrin deposit in glomerular. In CLP model , curcumin inhibited decreased of platelets at 6hr but the amount of fibrinogen still decreased .These results revealed the therapeutic potential of curcumin in the coagulative-inflammatory cascade of endotoxemia or severe infection. It is suggested that curcumin may be useful to prevent DIC induced by infection.