臺灣博碩士論文加值系統

Klebsiella pneumoniae (KP) 是在東亞及南亞最常見造成肝膿瘍的病原體，而糖尿病史一個主要的危險因子．為研究KP菌造成肝膿瘍的機制以及可能的以及可能的改善方式，我們使用STZ小鼠及Akita小鼠 (C57BL/6J-Ins2Akita)．發現在糖尿病鼠中KP菌由腸道易位到肝臟量增加，可能致病菌Enterococcus以及E.coli過度生長，而益菌lactobacilli/bifidas在腸道中卻減少，腸道菌量增加可能是因為腸道通透性變化，使用多光子顯微鏡在活體小鼠身上觀察，發現的確在STZ-DM的小鼠身上腸道通透性增加，且杯狀細胞的數量也增加，而經由杯狀細胞穿透的量比從細胞間隙來得多，而餵食FOS後可以回復這個狀況，使得通透性下降．且餵食小鼠Fructooligosaccharides (FOS)或是 dead L. salivarius (dLac) 可以改變高血糖所造成的腸道菌叢失衡，並腸內菌轉位到肝臟的量也顯著下降．
小鼠血中ALT濃度增加且肝臟細菌的清除能力也下降，腸道中的iNOS protein表現增加，Kupffer cells中的IL-1β及TNF-α 表現增加進而增強發炎反應及肝臟的傷害．然而餵食小鼠Fructooligosaccharides (FOS)、 dead L. salivarius (dLac) 或iNOS抑制劑（L-NAME）後在糖尿病鼠上可減少腸道iNOS 蛋白的表現及Kupffer cell的活化，並且增加肝臟對KP菌的清除力．
總的來說，高血糖引發細菌腸道失衡及iNOS表現而NO產物增加，KP細菌易位增加，而餵食FOS、dead L. salivarius 及Ｌ-NAME可有效減少高血糖所引起的菌叢失衡、腸道iNOS表現及細菌易位．

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of hyperglycemia on KP liver abscess was examined in streptozotocin- induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1β and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed hyperglycemia-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. iNOS inhibition with L-NAME decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases hyperglycemia-induced intestinal iNOS expression and KP liver translocation. Hyperglycemia induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production.
Enteric dysbiosis might result in gut barrier dysfunction via permeability increased. Using multiphoton microscopy observed the intravital mice, we found the intestinal permeability increased in STZ-DM mice and the goblet cells ratio also increased. More interesting, the FD4 leakage via goblets cell is more than paracellur space or gaps. Feeding FOS could reverse that situation, but it can’t change the distribution about of leaks in goblet cells and paracellular spaces.

誌謝……… i
中文摘要……… ii
English Abstract………iv
目錄……… vi
圖目錄……… vii
表目錄……… viii
第一章 前言……… 1
第一節 介紹……… 1
第二節 研究目的……… 7
第二章 實驗方法……… 8
第一節 實驗介紹……… 8
第二節 實驗方法細則……… 11
第三章 實驗結果………18
第四章 討論……… 28
參考文獻………72

List of Figures
FIGURE 1………79
FIGURE 2………79
FIGURE 3………80
FIGURE 4………80
FIGURE 5………81
FIGURE 6………81
FIGURE 7………81
FIGURE 8………82
FIGURE 9………83
FIGURE 10………85
FIGURE 11………87
FIGURE 12………89
FIGURE 13………91
FIGURE 14………93
FIGURE 15………95
FIGURE 16………97
FIGURE 17………99

List of Tables
Tables of introduction
TABLE 1 ………77
TABLE 2………78

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