| Summary: | 碩士 === 國立中山大學 === 生物科學系研究所 === 102 === Diabetic patients with pyogenic liver abscesses caused by Klebsiella pneumoniae (K. pneumoniae) usually found in Taiwan but the pathogenic mechanism for this observation is still unclear. It is known a vast array of microbes reside in human intestine and their composition are closely related to host’s immunity. Thus, diabetic C57BL/6 mice induced by streptozotocin were used to investigate the correlation between liver injury progression and changes of intestinal microbiome as well as immunity. When diabetic mice were induced for a month, the results revealed that liver injury was occurred according to increased plasma ALT levels and decreased hepatic bacterial clearance, in addition, intestinal bacteria overgrowth, enteric dysbiosis, increased intestinal bacterial translocation especially pathogenic K. pneumonia, and dysfunctional mucosal immune system were also observed. However, treating with the probiotic, Lactobacillus salivarius or the prebiotic, fructo-oligosaccharides could significantly improve the broken intestinal homeostasis, restored mucosal antibacterial protein, and lessened liver injury progression in diabetic mice. Moreover, increased intestinal iNOS activity and nitrate as well as endotoxin in portal vein were restored not only by probiotic and prebiotic but also by pharmacological inhibitor of iNOS, L-NAME in diabetic mice. Then, through decreasing IL-1β expression in Kupffer cells by L-NAME, hepatic bacterial clearance was significantly restored in diabetic mice. Therefore, iNOS may be a useful target for prevention of liver injury progression in diabetic patients.
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