2012-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649313摘要：腹腔內粘黏(intra-abdominal adhesions)為腹部手術後常見的病發症，雖然造成腹部粘黏的致病機轉至今仍然不完全了解，但一般認為因為創傷、感染或缺血所產生的腹部傷害，會引發立即性的發炎反應，之後會伴隨有血管通透性的增加和分泌富含纖維蛋白(fibrin)的滲出液。如果纖維蛋白不能即時且完全的被纖維溶解酵素原/纖維溶解酵素(plasminogen/plasmin)系統移除，將會引起膠原蛋白(collagen)沉積在蛋白多醣和纖維網質(proteoglycan and fibronetin)上，最後導致粘黏的形成。我們91年國科會計畫(NSC91-2314-B002-244)以空腸磨擦方式製造小腸粘黏模型，研究腹部粘黏對基因表現的影響，同時以microarray方法檢驗基因的變化。研究發現結果發現1.5%的基因有明顯改變，其中74種基因強度增加，19基因強度減少，而血中neuropeptide Y濃度明顯增加(發表在Wound Repair and Regeneration)。腹腔內粘黏的發生和基因變化是有相關，這些有相關的基因大概可分為四大類，第一種和發炎、防護以及壓力有關；第二種和細胞蛋白質構造有關；第三種和細胞表面受體、生長因子和轉譯有關；第四種和細胞新陳代謝、蛋白質和成和轉換有關，這個結果發現發炎反應在粘黏形成的過程中佔重要的地位。我們93年國科會計畫(NSC 93-2314-B-002-260)證實低溫時發炎反應較小時，粘黏也會下降，此論文{Peritoneal Infusion with Cold Saline DecreasedPostoperative Intra-abdominal Adhesion Formation}已發表在World Journal ofSurgery，但文中仍有幾件事待解決，第一是何種溫度最好未知，我們國科會的計畫使用的是4℃冰食鹽水，但有低溫致死情形，第二是沖洗時間多久最好未知，是否沖洗越久越好也未知，再者是食鹽水沖洗較好還是乳酸林格氏液較佳或其他液體仍未知，本研究想解決上述的問題。此次我們仍用小鼠空腸磨擦方式製造粘黏的動物模式後，第一年在腹腔關閉前以10℃、15℃、20℃的食鹽水注入腹腔中15 分鐘，然後分別於外科手術後第一、七、十四天將小腸取出，先記錄其粘黏分數，比較不同低溫的效果，以找出最理想的低溫再做下一個實驗。在此溫度下比較不同液體的效果，包括normal saline、lactate Ringer、和6% Dextran-70，並檢驗對凝固功能PT、PTT、和INR 的影響，藉以找出最佳的浸泡液體。第二年研究以第一年找出的溫度和液體進行浸泡時間多久的研究，我們分別以浸泡15 分鐘、30 分鐘、和45 分鐘來比較對粘黏的影響，同時檢測影響fibrin 形成最重要二個因子的變化，包括tPA 和PAI-1 以及其活性變化等因子在低溫時的變化，了解他們在粘黏時的角色。因Pentoxifylline 在peritoneal dialysis 時文獻已報告可用來減少peritoneal fibrosis，粘黏也是fibrosis 的一種，第三年將給與Pentoxifylline來檢視腹腔內粘黏的情形，希望找出好的方法以減少手術後腹腔內粘黏的現像，將來可廣泛使用在臨床上來嘉惠腹部手術患者。<br> Abstract: Intra-abdominal adhesion is a common complication after abdominal surgery。Although the mechanism of postoperative intra-abdominal adhesion formation isnot completely clear，trauma、infection or ischemia resulted in abdominal injurywill induce inflammatory reaction and followed by exudates secretion includingfibrin formation。If fibrin can not be completely removed by plasminogen/plasminsystem，collagen will deposit on proteoglycan and fibronetin and finallyformation of adhesion。Our 2002 NSC project (NSC91-2314-B002-244) used jejunumabrasion model to study the gene changed after adhesion formation。We usedmicroarray to screen the changed gene and found that 1.5% of gene changed afteradhesion formation，including seventy-four genes is up regulated and nineteengenes down regulated (published at Wound Repair And Regeneration)。These genescan be divided into four groups: First group of gene is associated withinflammation，protection and stress；Second group of gene is associated withcellular protein structure；Third group of gene is associated with surfacereceptor、growth factor and cell translation；Fourth group of gene is associatedwith cell metabolism，protein synthesis and translation。These results foundthat inflammation is strongly related with adhesion formation。Our 2004 NSCproject (NSC 93-2314-B-002-260) proved postoperative hypothermia will decreasethe condition of inflammation and the adhesion formation also decreased. Ourpaper {Peritoneal Infusion with Cold Saline Decreased PostoperativeIntra-abdominal Adhesion Formation} has been published at World Journal ofSurgery。But，there are some issues needed to be resolved。First，we used 4℃ normal saline resulted in 2 deaths due to hypothermia。The most approximatetemperature of cold fluid is still unknown。Second，we used 4 ℃ normal salinefor peritoneal infusion for 30 min。Whether the longer the peritoneal infusion，the less the adhesion is unknown。Third，saline was reported to have adhesiogeniceffect。Whether the other kind of fluid is superior to saline for peritonealinfusion is unknown。This study also used jejunal abrasion model as previous study。The first year，before the closure of abdominal wall we will use 10℃，15℃，and 20℃ cold normalsaline to irrigate the abdominal cavity for 15 min。The animal will be sacrificedat postoperative day 1，day 7 and day 14 to check the score of adhesion。Afterwe find the suitable temperature, we will continue to test the suitable fluidfor peritoneal infusion。We will use normal saline, lactate Ringer and 6%Dextran-70 to irrigate abdominal cavity and compare their effect ofpostoperative adhesion。The second year，we will determine how long of peritonealinfusion is suitable for adhesion prevention and also test the influence oftPA and PAI-I on the fibrin formation and adhesion formation。Pentoxifyllinehas been reported to decrease peritoneal fibrosis during peritoneal dialysis。The third year，we will explore the effect of Pentoxifylline on the postoperativeadhesion formation。We hope to find the best fluid，temperature and durationto irrigate abdominal cavity and apply it in clinical practice to decreasepostoperative intra-abdominal adhesion formation in the near future。腹腔內粘黏食鹽水乳酸林格氏液低溫腹部手術Intra-abdominal adhesion formationnormal salinelactated Ringerabdominal surgery