2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/655008摘要：腸道屏障主要包含了腸道表皮細胞及細胞與細胞間隙間的緊密結合複合物，用以保護個體不受外來有毒物質及病菌的入侵。細菌感染會引發腸道表皮細胞的凋亡並傷害細胞間緊密結合蛋白，進而破壞腸道屏障。 肥胖與腸內菌有關，並會增加腸道通透性。減重手術是目前證實針對嚴重肥胖的病人，唯一可以長期有效控制體重的治療方法；近來的研究發現，減重手術中的胃腸繞道手術會改變腸內菌種、小腸絨毛的高度和深度，以及增加腸道細胞的增生。目前為止，高脂飲食、胃腸繞道手術及腸道屏障間的關聯尚未明朗，因此，我們假設高脂飲食及胃腸繞道手術會改變腸道屏障。 我們規劃了一個三年計畫。在計畫的第一年，三十隻餵食一般飼料的大鼠會被隨機分成十二指腸空腸繞道手術組或假手術組。在接受十二指腸空腸繞道手術後，小腸會被分成三段：食物段、膽胰段及混合段。我們會比較測量兩組間的腸內菌數目及血清中的內毒素濃度，分析食物段、膽胰段、混合段、盲腸及大腸上的腸道通透性、細菌轉位量多寡及細胞緊密結合蛋白的表現量，以及血清中細胞緊密結合蛋白的表現量；此外，也會分析比較食物段、膽胰段、混合段及大腸的組織病理變化和腸道細胞增生及凋亡指標的表現量差異。 在第二年，三十隻餵食高脂飼料的大鼠會被隨機分成十二指腸空腸繞道手術組或假手術組。而在第三年，三十隻大鼠會被隨機分成一般飼料組或高脂飼料組。在第一年施行的各項實驗，都會在第二及第三年再次施行，以用來測量分析腸內菌及腸道屏障的改變。 在匯集了本計劃的三年結果後，我們預期可以釐清高脂飲食、十二指腸空腸繞道手術和腸道屏障的關聯，本計劃的成果可以有助於了解肥胖、肥胖相關疾病、減重及十二指腸空腸繞道手術的可能致病及治療機轉。 <br> Abstract: The gut barrier, including tight junctional complex and the dynamic balance between epithelial cell proliferation and apoptosis, forms a defense layer against noxious substances and pathogens into body. Bacterial infection would induce excessive epithelial cell death and damage tight junctional proteins, and then change gut barrier. Obesity is associated with gut microbiota and increased intestinal permeability. Bariatric surgery is the only effective method for severely obese individuals to maintain long-term weight loss. Recent studies disclose gastrointestinal bypass, one of bariatric surgery, changes gut microbiota, villus height, crypt depth, and proliferation indices in intestine. To the best of our knowledge, the association among high fat diet, gastrointestinal bypass, and gut barrier has not been described previously. Therefore, we hypothesize high fat diet and gastrointestinal bypass would disrupt gut barrier. In the first year of this three year project, 30 8 weeks old male SD rats fed with normal chow will be randomly divided into duodenojejunal bypass (DJB) and shame operation (SO) groups. The small intestine will be divided into three parts: alimentary limb, biliopancreatic (BP) limb, and common limb after DJB. Intestinal microbiota and systemic endotoxin level will be measured. Gut permeability in alimentary limb, BP limb, common limb, cecum, and colon will also be evaluated by Ussing chamber, analyses of bacterial translocation, and western blotting of tight junctional proteins. Change of intestinal permeability will also be evaluated by measurement of serum zonulin level. Besides, histopathology of intestine, including alimentary limb, BP limb, common limb, and colon, and western blotting for the expression level of cell proliferation and apoptosis marker in intestine will be evaluated. The difference of the factors mentioned above between DJB and SO will be analyzed. In the second year, 30 8 weeks old male SD rats fed with high fat diet will be randomly divided into DJB and SO groups. In the last year, 30 8 weeks old male SD rats will be randomly divided into lean and diet induced obesity groups. Change of gut microbiota and pathophysiological change of gut barrier will also be evaluated in the second and third year. After pooling the three year results in this project, the relationship among high fat diet, duodenojejunal bypass, and gut barrier will be clarified. It would be helpful to discover the possible mechanisms of obesity, obesity related disorder, weight loss, and gastrointestinal bypass.高脂飲食十二指腸空腸繞道手術腸道屏障腸道通透性大鼠high fat dietduodenojejunal bypassgut barriergut permeabilityrat