The Role Of Intestinal Endotoxemia In High-sucrose And High-Fat Diet Induced NAFLD

[Objective] (1)To investigate the role of intestinal endotoxemia(IETM) in nonalcoholic steatohepatitis(NASH) induced by high-sucrose and high-fat diet;(2) To investigate the role of IETM in NASH developed hepatic fibrosis.[Methodes] 48 male Wistar rats were randomly divided into normal control group(N group) (n=24) and high-sucrose and high-fat group(G group)(n=24), then randomly divided the two groups into 1 month,2 months,3 months and 6 months. Each group was killed as plannedat the end of 1 month,2 months,3 months and 6 months to collect blood of abdominal aorta and hepatic tissue. The levels of alanine transaminase(ALT),endotoxin(LPS), tumor necrosis factor( TNF-a), interleukin-10(IL-10),adiponectin(APN), triglyceride(TG), monocyte chemoattractant protein-1(MCP-1),fasting plasm glucose (FPG), fasting plasm insulin(FINS) in the serum were measured,and the insulin resistance index(IRI) was calculated;the TG and hydroxyproline(HYP) of hepatic homogenate was exmined;The liver specimens were prepared for HE staining and Van Gieson(VG) staining,and the changes of histology were observed.[Results] (1) The 1 month and 2 months:Compared with normal control groups,the levels of ALT,LPS,TNF-α,TG,FPG, FINS and IRI in the serum of high-sucrose and high-fat group of 2 months were higher, the TG of hepatic homogenate was higher,but the levels of APN and IL-10 reduced,and the differences had statistic significance(P<0.05).HE staining revealed that the model group of 1 month show small lipid droplets mainly,no ballon degeneration, and there were little inflammory cells infiltrating in hepatic lobules and portal areas,no degeneration and necrosis; the model group of 2 months show large lipid droplets mainly, ballon degeneration were presented,and there were lots of inflammory cells infiltrating in hepatic lobules and portal areas, degeneration and necrosis were existed.(2) The 3 months and 6 months:Compared with normal control groups,the levels of ALT, LPS,TNF-α,MCP-1,FPG, FINS and IRI in the serum of high-sucrose and high-fat group were higher, and the differences had statistic significance(P<0.05);Conpared with the model group of 3 months,the HYP of hepatic homogenate of 6 months was higher, and the differences had statistic significance(P<0.05).VG staining revealed that the model group of 3 months show some fine fiber bundle from central veins extending into hepatic lobules,but no fiber septas; the model group of 6 months show some wide fiber septas,which broke the limiting plate and enclosed the hepatic lobules,some areas of the hepatic tissue had pseudolobule.[Conclusion] (1) NASH and diabetes mellitus in rats can be induced by high-sucrose and high-fat diet,the mechanism of which possibly is related to the LPS induced insulin resistance and the imbalance and interaction between some factors such as TNF-a, IL-10 and APN.(2) LPS plays a very important role in the process of NASH developing into fibrosis.The mechanism could be that LPS can activate the adipocytes in adipotic tissue to release lots of pro-fibrosis cytokines(e.g. TNF-a) to initiate and promote the occurrence and development of hepatic fibrosis.