摘要
Objective:To explore the variations of intestinal flora in alcoholic fatty liver (AFL) and study the possible role of intestinal flora in AFL.Methods: Forty-five male C57BJ/6 mice were randomly divided into three groups: control group (NC), 10%v/v alcohol group, 20%v/v alcohol group (15 per group) with food and water available ad libitum for 24 weeks, and the model of AFL was induced by long-term and chronic drinking. Human hepatocyte lines (LO2 cells) were incubated with different concentrations of alcohol and LPS for 24 h. The relative abundance of intestinal flora was detected by high-throughput Illumina sequencing. The levels of ethanol, LPS, ALT and AST in serum were detected, and glucose tolerance test (GTT) was performed after fasting. Liver lipid deposition was detected by oil red'O' staining, and liver morphology was observed by H&E staining to verify the AFL model. The expression of NLRP3 and IL-1β in LO2 cells were detected by Western-blot.Results: Compared with NC group, the level of ethanol in serum from two drinking groups was significantly elevated, and the levels of LPS and AST in serum from 20%v/v alcohol group were significantly increased, while there was no difference in the level of ALT. The relative abundance of Bacteroidetes/Firmicutes in intestinal flora of 20%v/v alcohol group was significantly increased, compared with NC group. Moreover, the expression of NLRP3 and IL-1β were up-regulated after exposure to LPS and alcohol.Conclusion: Long-term and chronic drinking could result in an imbalance of intestinal flora and contributed to an increase of LPS in serum. We speculated both alcohol and LPS involved in the pathogenesis of ALF by activating NLRP3 inflammasome to release pro-inflammatory factor IL-1β.
