The Mechanism Of Probiotics Preventing Thioacetamide-induced Liver Fibrosis In Rats

BackgroundThe essence of liver fibrosis is a wound-healing response to liver damage and inflammation.As the common pathological stage for various chronic liver disease,the process is completelyreversible. In recent years, more and more attention on the interaction between liver disease andintestinal endotoxemia are paid.The secondary liver damage caused by IETM play a importantrole in the progress of liver disease. Some reports pointed out that IETM might participant inpromoting liver fibrosis. The major endotoxin receptor CD14 plays a critical role in endotoxinsignal transduction and Kupffer cells activation. Probiotics agents Bifid Triple Viable andBacillus Licheniformis are commonly used in clinical.The studys about that Bifid Lriple Viablecan reduce plasma endotoxin have been reported, and its mechanisms of the action as known atpresent are related to supplement of dominant bacteria, reconstruction of intestinal microflorabalance and to restore intestinal mucosa barrier. Bacillus Licheniformis also can regulateintestinal flora better, however the study about the effect of Bacillus Licheniformis on plasmaendotoxin is rarely reported. In order to make clear the effect of Bifid Triple Viable and BacillusLicheniformis on the level of plasma endotoxin respectively, and to investigate the preventiveeffect and possible mechanism of probiotics on liver fibrosis induced by thioacetamide inrats ,we conducted this research program.ObjectiveTo investigate the effect and possible mechanism of probiotic agents in preventing liverfibrosis , by studying the change of the plasma endotoxin level in liver fibrosis rats treated withBifid Lriple Viable or Bacillus Licheniformis.MethodsFifty rats were randomly divided into 5 groups equally: control group (N), TAA modelgroup (T)，Bacillus Licheniformis low-dose group (LZ)，Bacillus Licheniformis high-dosegroup (HZ) and Bifid Lriple Viable group (P).The model of rats with liver fibrosis was inducedby subcutaneous injection of thioacetamide (TAA), and given corresponding dose probioticagents by gastric perfusion simultaneously rsepectively as the group LZ, the group HZ and thegroup P. The level of plasma endotoxin(ET),alanine aminotransferase (ALT),aspartateaminotransferase (AST),lactic dehydrogenase (LDH), malondialdehyde (MDA) were measured. HE and Picrosirius red staining were used to assess pathomorphology changes andcollagen content.The expression of CD14 in rats liver tissue was tested byimmunohistochemistry methods.Results(1) The HE and Picrosirius red staining analysis：Comparing with Group T,the percentagesof liver damage area in Group LZ, Group HZ and Group P were significantly decreased(29.71.%±6.58% vs 53.93%±9.76%，25.79%±6.76% vs 53.93%±9.76%，30.13%±7.80% vs53.93%±9.76%，F=74.896, P<0.01). The contents of collagen fiber were significantly higherin Group T than in Group N,Group LZ,Group HZ and Group P（0.06%±0.04% vs1.44%±0.59%，0.60%±0.19% vs 1.44%±0.59%，0.19%±0.83% vs 1.44%±0.59%，0.17%±0.52% vs 1.44%±0.59%，F=39.919，P<0.01）.(2) The plasma endotoxin, serologic index analysis：The levels of ET,ALT,AST,LDH andMDA in Group N,Group LZ,Group HZ and Group P were significantly lower than in Group T（ET：0.07±0.03 vs 0.25±0.12，0.08±0.04 vs 0.25±0.12，0.09±0.03 vs 0.25±0.12，0.10±0.03 vs 0.25±0.12，F=21.627，P<0.05；ALT：5.98±2.80 vs 12.60±2.77，5.95±2.80vs 12.60±2.77，6.00±4.06 vs 12.60±2.77，6 .98±3.40 vs 12.60±2.77，F=8.012，P<0.05；AST：13.80±2.73 vs 21.83±2.41，16.93±1.88 vs 21.83±2.41，15.00±1.94 vs 21.83±2.41，16.65±1.55 vs 21.83±2.41，F=22.764，P<0.05；LDH：2596.89±533.75 vs 3982.38±813.90，2744.04±670.15 vs 3982.38±813.90，3318.14±555.54 vs 3982.38±813.90，3321.24±633.36vs 3982.38±813.90，F=7.194，P<0.05；MDA：2.83±0.57 vs 5.03±0.76，3.43±0.37 vs 5.03±0.76，3.56±0.54 vs 5.03±0.76，3.55±0.575 vs.03±0.76，F=19.871，P<0.05）.(3) The immunohistochemical staining analysis：The expression of CD14 in liver tissue ofGroup LZ,Group HZ and Group P were significantly lower than in Group T（2.35±1.64 vs24.55±12.49，0.26±0.25 vs 24.55±12.49，0.21±0.11 vs 24.55±12.49，F=36.311，P<0.01）.Conclusions(1) Probiotics could prevent the formation of intestinal endotoxemia in rats induced byTAA.(2) Probiotics could correct disturbance of hepatic microcirculatory and improve liverfunction，by inhibiting the formation of intestinal endotoxemia.(3) Probitotics could prevent liver fibrosis formation to some extent. The mechanisms maybe associated with that probitotics relieve intestinal endotoxemia and downregulation of CD14expression to stop liver injury from endotoxin.