臺灣博碩士論文加值系統

短腸症候群患者需依賴全靜脈營養(TPN)維持生命，但長期使用TPN亦造成腸萎縮、免疫不全及細菌轉移引發菌血症等問題。研究指出益生菌具有維持腸道完整及調節免疫的功效；益生原經益生菌發酵產生短鏈脂肪酸可作為腸上皮細胞能量來源；且雲芝胞外多醣肽(Trametes versicolor extracellular polysaccharopeptides，TV-ePSP)具抗發炎及免疫調節的功能。本研究探討單獨或合併補充益生菌、木寡糖(XOS)及TV-ePSP對使用TPN輸液之SBS大鼠發炎反應及腸道菌相的影響。雄性SD大鼠除正常對照組外，其餘六組施予十二指腸懸韌帶後端10公分至大腸前端5公分的腸道切除及右頸靜脈插管手術。術後一天開始管餵去離子水、益生菌(Lactobacillus acidophilus及Bifidobacterium bifidum各10的9次方CFU)、TV-ePSP (1 g/kg)、益生菌與TV-ePSP、益生菌與XOS (500 mg)、或益生菌、XOS與TV-ePSP混合物。灌餵六天之結果顯示，單獨補充益生菌顯著降低短腸症增加的血漿NOx濃度、空腸損傷、肝臟IFN-r與肺臟IL-8含量及肝臟、腎臟與脾臟的重量；單獨補充TV-ePSP顯著降低短腸症增加的血漿IgA與NOx濃度及空腸損傷與IFN-r含量，且顯著增加短腸症降低的空腸絨毛長度；合併補充益生菌與TV-ePSP顯著增加短腸症降低的血漿IL-6濃度，且顯著增加乳酸產生菌Enterococcus屬之豐度；合併補充益生菌與XOS顯著增加短腸症降低的結腸Firmicutes門階層下Clostridiales目之豐度；三者合併補充顯著增加短腸症降低的腸道菌相之物種多樣性，且顯著增加丁酸產生菌Blautia屬之豐度。綜上所述，合併補充益生菌及TV-ePSP具有緩解短腸症誘導之腸道損傷及發炎反應，並增加腸道乳酸菌的生長。

Patients with short bowel syndrome (SBS) require total parenteral nutrition (TPN) to sustain their life; however, long-term use of TPN may result in intestinal atrophy, immune dysfunction, bacterial translocation and further lead to bacteremia. Studies showed that probiotics have the abilities to maintain intestinal integrity and modulate immune response. In addition, prebiotics can be fermented by probiotics to produce short chain fatty acids that provide energy for the epithelial cells of the intestine. Moreover, Trametes versicolor extracellular polysaccharopeptides (TV-ePSP) have anti-inflammatory and immune modulatory activities. In the present study, we aimed to investigate the effects of single or simultaneous, oral supplementations of probiotics, xylooligosaccharides (XOS) and TV-ePSP on inflammatory response and gut microbiota in SBS rats with TPN infusion. Male SD rats, except those in the control group, were performed with bowel resection from 10 cm beyond the ligament of Treitz to 5 cm proximal colon and catheterization in the right jugular vein. One day after the surgeries, the SBS rats were orally administered with deionized water, probiotics (10 9 CFU of Lactobacillus acidphilus and 10 9 CFU of Bifidobacterium bifidum), TV-ePSP (1 g/kg), probiotics and TV-ePSP, probiotics and XOS (500 mg/day) or the combination of probiotics, XOS and TV-ePSP daily for 6 days. The results showed that single supplementation of probiotics significantly decreased the SBS-increased plasma nitrite/nitrate, jejunal damage, hepatic interferon (IFN)-r, pulmonary interleukin (IL)-8, and the liver, kidney and spleen weights; single supplementation of TV-ePSP significantly decreased the SBS-increased plasma plasma nitrite/nitrate and immunoglobulin-A and jejunal damage and IFN-r, as well as increased the SBS-decreased villus height in the jejunum; combination of probiotics and TV-ePSP significantly increased the SBS-decreased plasma IL-6 and increased the abundance of Enterococcus genus, the lactate-producing bacteria; combination of probiotics and XOS significantly increased the SBS-decreased abundance of Clostridiales of the Firmicutes phylum; and combination of probiotics with TV-ePSP and XOS significantly increased the SBS-decreased bacterial diversity and increased the abundance of Blautia genus, butyrate-producing bacteria. In summary, combination of probiotics and TV-ePSP may have the abilities to alleviate the SBS-induced intestinal damage and inflammatory response and may increase the growth of lactate-producing bacteria.

摘要 I
Abstract III
致謝 V
目錄 VI
表目錄 IX
圖目錄 X
縮寫 XII
第一章 序言 1
第二章 文獻回顧 3
第一節 短腸症候群 3
第二節 病理機制 5
一、生理變化 5
二、腸道屏障與通透性 7
三、發炎反應 8
四、氧化壓力 11
五、腸道菌相失衡 12
六、細菌過度生長與轉移 13
七、腸道適應性 15
第三節 臨床營養支持 16
一、全靜脈營養 17
二、全靜脈營養之併發症 18
三、全靜脈營養造成的腸衰竭相關肝臟疾病 19
第四節 輔助性治療 21
一、益生菌(Probiotics) 22
二、益生原(Prebiotics) 27
三、共生質(Synbiotics) 30
四、雲芝胞外多醣肽 32
第三章 假說與目的 36
第四章 材料與方法 38
第一節 研究架構 38
一、實驗動物 38
二、手術模式 38
三、實驗設計 39
第二節 分析項目 40
一、體重及組織重量 41
二、血球計數及血液生化值 41
三、空腸質量及免疫球蛋白A 41
四、空腸的型態變化 42
五、全身及局部發炎媒介物 43
六、菌相分析 44
第三節 統計分析 46
第五章 結果 48
第一節 大鼠體重與組織器官的重量 48
第二節 血球計數及血液生化值 51
第三節 血漿發炎媒介物濃度 55
第四節 空腸組織型態、質量變化與損傷程度 59
第五節 空腸發炎媒介物含量 64
第六節 血漿與空腸黏膜層IgA 68
第七節 肝臟發炎媒介物含量 70
第八節 肺臟發炎媒介物含量 73
第九節 腎臟發炎媒介物含量 76
第十節 糞便菌相分析 79
一、腸道細菌群落結構之組內多樣性 79
二、腸道細菌群落之主座標分析 81
三、腸道細菌群落之物種相對豐度 83
四、腸道細菌群落之LEfSe分析 90
第六章 討論 94
第一節 益生菌、XOS及TV-ePSP對短腸症生理變化及腸道損傷之影響 94
第二節 益生菌、XOS及TV-ePSP對短腸症發炎反應之影響 97
第三節 益生菌、XOS及TV-ePSP對短腸症腸道菌相之影響 103
第七章 結論 109
第八章 參考文獻 110
附錄 A 124
附錄 B 129

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