AIM:To investigate the effect of lipopolysaccharides(LPS)preconditioning on CCl4-induced liver injury and the change of LPS signal transduction.METHODS:The male Wistar rats were divided randomly into liver-injury group,which were injected with CCl4 5 mL/kg first,three days later were injected 0.3 mL 40% CCl4 and 60% olive oil. Animals in LPS preconditioning group were injected with LPS 0.5 mg/kg before the day CCl4 was given. Rats received high fat diet were as liver injury group,and normal control group received normal diet. The lymphocytes infiltrated in the liver tissue were counted. The endotoxin and ALT level in rat plasma,TNF-? content and expressions of TLR4,p38,p-p38,I??,NF-?? in the rat livers were also determined.RESULTS:The lymphocytes in liver slice and ALT level of the plasma in LPS preconditioning group were lower significantly than those in the liver injury group,and the expressions of TLR4,p-p38,NF-?? in the liver were the same. In contrast,the expression of I?? was higher.CONCLUSION:LPS preconditioning relieves obviously CCl4-induced chronic liver injury. The mechanism may be associated with change of signal transduction of LPS,which results in decrease of pre-inflammatory cytokines.

ObjectiveTo investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA). MethodsEight healthy male specific pathogen-free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t-test was used for comparison of differentially expressed miRNAs between two groups. ResultsThe principal component analysis showed that the inter-group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as “DNA binding” (P=1.47×10-6), participated in the biological processes such as “transcription, DNA-templated” (P=2.36×10-7), and were mainly enriched in the cellular components such as “neuronal cell body” (P=5.99×10-6), while the target genes of the downregulated miRNAs had the molecular functions such as “RNA polymerase II proximal promoter sequence-specific DNA binding” (P=2.49×10-6), participated in the biological processes such as “regulation of transcription, DNA-templated” (P=1.64×10-11), and were mainly enriched in the cellular components such as “nucleoplasm” (P=4.30×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in “Endocytosis” (P=0.000 4), while the target genes of the downregulated miRNAs were mainly enriched in the “Hippo signaling pathway” (P=0.004), and the above functional analysis results were statistically significant (P＜0.05). ConclusionThere are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH.

Objective : To study the mechanism of the treatment of metabolism associated steatohepatitis ( MASH) in rats with Xiaoyao Wan． Methods : Twenty-four SD male rats were randomly divided into control group ( CON group，n = 8) and model group ( n = 8 ) ．The model group was given high-fat diet ，carbon tetrachloride ( CCl4 ) subcutaneous injection，hunger and satiety disorder and tail clamping for four weeks to establish the MASH model， and the rats were randomly divided into the MOD group and the Xiaoyao Wan group (XYW group) ，with 8 rats in each group．The rats of the XYW group were given Xiaoyao Wan，the other two groups were given normal saline. Four weeks after administration ，the serum biochemical indexes and oxidative stress indexes of rats in different groups were detected．The pathological sections of rat liver tissue were observed by hematoxylin-eosin ( HE) stai- ning and oil red O staining．The expression of cytochrome P450 2E1 ( CYP2E1) ，factor-related apoptosis ligand (FasL) ，tumor necrosis factor-α ( TNF-α) and tumor growth factor-β1 ( TGF-β1 ) in rat liver were detected by Western blot method．The relative contents of CYP2E1，FasL，TNF-α and TGF-β1 mRNA in liver tissue were de- tected by RT-qPCR. Results : The general condition of rats in the XYW group was significantly improved compared with the MOD group ; the level of hepatic index was significant decrease compared with the MOD group (P＜0. 01) and the level of body mass index was significant increase compared with the MOD group (P ＜0. 01) ; the serum levels of triglyceride ，total cholesterol ，low －density lipoprotein cholesterol ，aspartate aminotransferase ，alanine aminotransferase，malondialdehyde，monocyte chemotactic protein-1，TNF-α , and interleukin (IL) -18 were signif- icantly reduced compared with the MOD group (all P＜0. 05) ，and the levels of high－density lipoprotein choles- terol，superoxide dismutase，and IL-10 were significantly elevated compared with the MOD group (all P＜0. 05) ; the content of lipid droplets in hepatocytes of rats was significantly reduced compared with the MOD group under light microscope ; the protein levels of CYP2E1，FasL，TNF-α and TGF-β1 in liver tissues were significantly re- duced compared with the MOD group ( all P ＜0. 05 ) ，and the relative contents of CYP2E1 ，FasL，TNF-α and TGF-β1 mRNA were significantly reduced compared with the MOD group ( all P ＜0. 05) ． Conclusion Xiaoyao Wan can regulate the expression of CYP2E1，FasL，TNF-α and TGF-β1 in the liver tissue of MASH rats by reduc- ing the accumulation of fat in the liver，so as to achieve the purpose of treating MASH.