最豐富的腸道菌存於腸道的末端部分，且大多數都是Gram-negative anaerobes。Toll-like receptors(TLRs)為一個可辨識腸道共生菌的系統，其中一個"病原體辨識分子" Toll-like receptor4(TLR4)主要辨識Gram-negative bacteria的lipopolysaccharide (LPS)並能引起發炎反應。在先前的研究報告指出，腸道菌可以增加宿主對細菌入侵時的抵抗能力，但其機制尚不清楚，本研究探討腸道菌被清除後TLR4表現與發炎反應間之關係，利用老鼠餵食抗生素四個星期來清除腸道菌，其中一部份在第三星期給予LPS刺激腸道的TLR4釋放，之後再給予燙傷引起發炎反應，結果發現燙傷24小時後的老鼠腸道通透性增加，細菌轉位至淋巴結的現象增加，肺組織中嗜中性白血球含量增加。燙傷24小時後腸黏膜的NFκB活性增加，HSP70和TLR4的表現增加，肺組織和腹腔吞噬細胞的TLR4表現增加，而腹腔吞噬細胞ICAM、TNF-α的表現也增加。然而，在餵食抗生素後再燙傷的老鼠，其腸黏膜的TLR4、ICAM、HSP70的表現減少，NFκB的活性降低，肺組織嗜中性白血球含量明顯降低，腹腔吞噬細胞的吞噬能力下降及TLR4、ICAM、TNF-α的表現減少。有趣的是，當老鼠給予LPS後，可回復因餵食抗生素所造成之影響，減少細菌轉位至淋巴結的現象，增加肺組織嗜中性白血球的含量及增加腹腔吞噬細胞的吞噬能力等，推測LPS啟動TLR4的辨識功能，降低傷害並增加吞噬細胞的吞噬能力及增加宿主對抗細菌的能力。因此腸道菌活化TLR4是增加宿主抵抗能力的主要關鍵，即腸道菌主要是經由TLR4發出信號誘發小鼠的防禦反應。

The most abundant microflora is present in the distal parts of gut and the majority of the bacteria are Gram-negative anaerobes. Toll-like receptor 4 (TLR4), one of the “pathogen-recognition molecules”, recognize the lipopolysaccharide (LPS), derived from Gram-negative bacteria. TLR4 recognized the intestinal microflora and triggers the inflammatory responses. Although the effect of intestinal microflora on enhancing host to response the challenge from bacteria has been established, the mechanism has not been well studied. In this study, the relationship between TLR4 expression and the inflammatory response under intestinal microflora depletion was investigated. Mice fed with antibiotics for 4 weeks to delete the intestinal commensals and supplemented with or without LPS to stimulate TLR4 at week 3 were under sham or burn treatment. Results showed that thermal injury intestinal permeability, bacterial translocation to mesenteric lymph nodes, and neutrophil deposition in lung. Also, the activation of NF-ΚB, expression of HSP70 and TLR4 were induced in intestinal after thermal injury. Moreover, TLR4 expression was increased in lung and peritoneal cells, ICAM and TNF-α expression were increased in peritoneal cells after thermal injury. However, NF-ΚB activation, expression of TLR4, ICAM, and HSP70 were decreased in intestinal mucosa of mice with microflora depletion after thermal injury. Microflora depletion also significantly decreased the MPO activity in lung, and the phagocytic activity, the TLR4, ICAM, and TNF-α expression of peritoneal cells after thermal injury. Interestingly, LPS supplement reversed the effect of microflora depletion, suggest that intestinal microflora can trigger the host defense through TLR4 signaling pathway in thermal injured mice.

Abstract in Chinese…………………………………………………………4
Abstract in English………………………………………………………….5
Introduction…………………………………………………………………6
Materials and Methods……………………………………………………..12
Results……………………………………………………………………...19
Discussion………………………………………………………………….26
Figures……………………………………………………………………...33
References………………………………………………………………….46.

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