https://scholars.lib.ntu.edu.tw/handle/123456789/201199
Title: | 魚油(Fish oil)對全胃切除老鼠腸道及全身性免疫之影響 | Authors: | 林明燦 | Keywords: | 魚油;全靜脈營養;全胃手術;免疫;腸道免疫;腸相關淋巴組織;抗氧化作用;細胞免疫;細胞激素;接著分子;Fish oil (FO);Total Parenteral Nutrition (TPN);Total Gastrectomy;Immunity;Intestine Immunity;Gut Associated Lymphoid Tissue (GALT);Antioxidant;Cellular Immunity;Cytokine;Adhesion Molecules | Issue Date: | 2005 | Publisher: | 臺北市:國立臺灣大學醫學院一般醫學科 | Abstract: | Total parenteral nutrition (TPN) is a milestone contribution to the surgical field since 1968 successfully tested in human. TPN is a life-saving modality and has improved the perioperative mortality and morbidity for patients with malnutrition undergoing surgery, espically in paitents with gastric cancer. Surgeons are encouraged to undertake aggressive radical surgery for gastric cancer only with good nutritional support. However, conventional TPN usually contains soy bean oil (SO), lacks many important nutrients, including fish oil (FO). Fish oil is the important nutrient for immune cells, and may suppress cancer cell. FO was reported to have some immunomodulation effect in septic subjects. FO supplemented TPN may enhance patient immunity, and may be the advancement of TPN in 21st century. However, the detailed mechanisms of FO-TPN effects on major surgery are unknown. Our previous studies investigated the influences of fish oil on the lipid metabolism in septic rats. However, it is unclear whether FO-TPN influences cytokine adhesion molecules production in rats after gastric surgery. One portion of this study is designed to investigate whether FO-TPN will influence antioxidant response, cellular immunity and cytokine production in rats following total gastrectomy. Rats are randomly divided into three group, standard total parenteral nutrition without fat (NO-TPN group, n=12), TPN with soy bean oil (SO-TPN group, n=12) or TPN with fish oil (FO-TPN group, n=12) after the gastrectomy. The nutrition fluid to each group is isocaloric (30 kcal/kg/D) and isonitrogenic (1.5 gN/kg/D) and fat in 30% of total calorie in the SO-TPN and FO-TPN groups. FO-TPN group receive 30% FO in total fat. Samples of blood are collected on preoperative day (Pre), post-operative day 3 (POD3). Systemic cytokine, adhesion molecules, antoxidant (SOD, GSH) and CD4, CD8, total lymphocyte in blood are determined. As surgical skill and perioperative care progress, surgeons are more aggressive in doing surgery for gastric cancers to obtain good treatment result. Radical aggressive surgery, eg total gastrectomy, may cause the more stressful insult to the patients, as compared with conventional conservative surgery. However, physiological responses of subjects to such stressful operation are not well understood. Recent studies revealed that cytokines, eicosanoids, and oxidative mediatorsare deeply involved in response to surgical stress. However, characteristics of systemic response influenced by FO-TPN undergoing total gastrectomy during perioperative period are not clarified. Small intestinal gut-associated lymphoid tissue (GALT) is a major contributor to primary immunologic protection at all mucosal sites. Approximately three fourths of the body’s immunoglobulin-secreting tissue locates on the gastrointestinal tract. In the model of total gastrectomy, gut is the main site of injury. Gut atrophy is frequently associated with many surgical insults, including sepsis, operation, etc. If FO has beneficial effect on improving mortality rate in sepsis as our previous reports stated, would FO enhances the systemic and mucosal immunity after gastrectomy? Another aim of this proposal is to investigate the effects of FO supplementation on intestinal and systemic immune response in rats with total gastrectomy. Total gastrectomy is considered to be a technique demanding, clinical relevant model of patients with gastric cancer. Because the mortality rate is high and sample collection is difficult in this animal model, this study is designed to be carried out cautiougly. FO will be administered by total parenteral nutrition after gastrectomy, to investigate the possible role of FO on gastrectomy. Animals are sacrificed 3 days after gastrectomy, a time point with severe inflammation in post-operative period, to investigate T cell and B cell population in GALT, spleen and blood. Besides, the ability of phagocytosis in peritoneal macrophage and blood leukocyte will also be evaluated. Plasma nutrient alteration, peritoneal NO concentrations, in vivo and in vitro cytokine secretion, intestinal sIgA production and cytokine mRNA expression in splenocyte will be analyzed. This study will be the first one to investigate the mechanisms of FO on GALT and systemic immunity in gastrectomy subjects. The results should be useful for understanding the effect of FO supplementation on modulating immune responses, and may have favorable effects for the patients undergoing major surgery. 全靜脈營養(Total Parenteral Nutrition ,TPN)是外科對整個醫學的一項劃時代重大貢 獻。只有在良好的營養醫療及支持(Nutrition therapy and nutrition support)之下,才能讓外科 醫師積極進行重大手術,達成治療目標,挽救病人性命,並且減少手術的併發症發生,甚 至有機會能減少癌症的再發。然而,傳統型的全靜脈營養(Conventional Standard TPN, SO-TPN)添加的脂肪(Fat emulsion)通常只含Soy bean oil (SO ,主要為w-6 fatty acid),缺乏 重要營養素w-3 fatty acids 如魚油(Fish Oil ,FO)。因此,在邁入21 世紀之初,傳統型的全 靜脈營養必需加以改良,讓全靜脈營養更趨完善。然而,FO-TPN 對生物體(Biology)及病人 (Patient)手術的影響機制所知有限,特別是FO-TPN 對全身(Systemic)及腸黏膜免疫(GALT) 方面影響的瞭解更是幾乎沒有。 添加魚油全靜脈營養(Fish Oil-supplemented TPN ,FO-TPN)是最近發展的改良型全 靜脈營養法之一。Fish Oil 是免疫細胞重要的營養素。目前魚油應用於大手術的研究仍然相 當有限,因此值得深入研究探討。Schauder P 等人發現魚油可調節大腸手術的IL-2 ,IFN-γ , TNF 反應,但對淋巴球的分類(Subset)無影響。Heller AR 等人研究發現腹部大手術病人給 予並不影響其凝血及血小板機能。Linseisen J 等人研究顯示病人腹部手術病人使用魚油並 無法改善血中脂肪的過氧化產物。然而Furukawa k 等人即發現進行食道切除大手術的病人 接受經口或經腸道魚油者可有效減輕IL-6 等發炎反應。因此,添加魚油對手術反應影響仍 不完全明暸。 隨著手術技術與周術期的照料(Perioperative care)的日益進步,愈來愈多的病人接受胃 癌手術的治療。手術是目前唯一可以有效治療胃癌的治療方式。因此,現代的外科醫師, 一方面要精進積極(Aggressive)與廓清性(Radical)的手術技術。也應該瞭解高壓力(High stress) 大手術(Major operation) 例如全胃切除術(Total Gastrectomy)對病人所產生的生理變化,更要 明瞭週術期營養醫療對胃切除病人的調節作用(Modulation)。 最近吾人等針對敗血症動物研究顯示,FO 可能會增進免疫細胞機能,甚至可能抑制癌 細胞。然而,以前關於FO 靜脈營養投與,幾乎沒有針對大手術時全身的免疫反應如抗氧 化,細胞激素,及接著分子影響作研究。添加FO 靜脈營養,如何影響全胃切除老鼠手術 術後的全身及腸道免疫,細胞激素,抗氧化作用,目前並不十分清楚。腸道淋巴組織(gut associated lymphoid tissue, GALT)是腸道及腸外組織重要的防禦系統,腸道內70-80%的免疫 球蛋白由腸黏膜淋巴組織產生以抵禦侵入腸道之致病原。有些報告顯示,手術可能會讓腸 道會受到黏膜萎縮的影響,因此在全胃切除大手術引致腸黏膜反應之實驗模式中,若FO 添加可增加全胃切動物之存活率,是否有可能因增強了腸道及全身性免疫反應而致。故本 實驗擬將老鼠以全胃切除,這是一種被認為最接近臨床上全胃切手術的動物模式,並在讓 老鼠胃切前以由口進食,胃切除後以全靜脈營養之輸入方式給與FO ,並與SO 組及NO 組 (完全不含fat)比較來研究FO 對胃切的影響,這將是第一個完整探討FO 對全胃切除時腸道 及全身性免疫反應之實驗。 由於本實驗所探討的免疫機制項目繁多,且動物實驗全胃切除手術之技術及執行困難 度高,要探討GALT 、脾臟、血液中T 及B 淋巴細胞之分佈比例,腹腔中巨噬細胞及全血 中白血球之吞噬能力等。並進一步分析血中營養素變化、腹水中cytokine 濃度、腸道中sIgA 之濃度、巨噬細胞及腸道、脾臟收集之淋巴細胞以體外刺激後之免疫反應。本計劃之研究 結果可瞭解FO 添加對全胃切除老鼠在術後最嚴重時期,腸道及全身性免疫反應之影響。 期望將來能對臨床胃切除手術高危險群病人有所助益,兼具基礎及臨床應用之雙重意義。 本研究可能發現與貢獻: c確定FO-TPN 如何影響胃切手術後全身及腸道免疫力,以及如何調節細胞激素,接著分 子,及抗氧化反應。 d將來展望:FO-TPN 可能對胃切手術的老鼠有調節全身及腸道免疫細胞激素及抗氧化作 用。因此,FO-TPN 可能應用於臨床讓病人安全的渡過手術期,含魚油的免疫營養 (Immunoutrition)應是將來外科領域的研究發展重點。 |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/22639 | Other Identifiers: | 932314B002256 | Rights: | 國立臺灣大學醫學院一般醫學科 |
Appears in Collections: | 醫學系 |
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