Investigations on Diabetes-related Kupffer cell activation and Klebsiella pneumoniae liver translocation

• Main Authors: Shu-Han Lin, 林姝含
• Other Authors: Lee-Wei Chen
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/z4jyff

碩士 === 國立陽明大學 === 急重症醫學研究所 === 105 === 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.