Objective To observe hepatocellular apoptosis and inflammatory cytokines expression and their mechanisms for lipopolysaeeharide (LPS)-induced acute liver failure in D-ga|actosamine (D-GalN)-sensitized rats. Methods Fifty-six rats were randomly divided into following groups: 0, 1, 2, 4, 6, 24 and 48 hours. 0 hour group served as control group and the rest did as treatment groups. The rats in the treatment groups received intraperitoneal injections of LPS (50 ng/g) and D-GaIN (300 μg/g) dissolved in 1 mL sterile 0.9% sodium chloride solution, while the rats in control group were treated with 1 mL sterile 0.9% sodium chloride solution only. The rats were sacrificed in the corresponding time points and their sera and liver tissues were collected. Liver tissues were fixed and stained with hematoxylin and eosin for optical microscopy examination. The serum cytokine expressions were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of tumor necrosing factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and p53 gene were detected by reverse transcriptase-polymerase chain reaction, and the 24 hours treated rats liver Caspase-3,8,9,12 activity were detected by chromogenie substrate method. Data for the experiments were expressed as x±s, and differences among means were compared using the analysis of variance. Results After drug treatment, liver tissues showed piecemeal necrosis and inflammatory cell infiltration, which significantly increased from 6 hours, 24 hours to 48 hours. The 1 hour treatment group with the highest concentration of TNF-α (727. 8 ± 261. 3) ng/L were significantly higher than the control group and other treatment groups(F= 49.82, P<0.01), 2 hours treatment group (156.4 ± 52.2) ng/L was significantly lower than the 1 hour group, but significantly higher than the control group (F = 30. 23, P< 0.01 ). But serum concentrations of IL-1β gradually increased, reaching the highest level in 24 hours group (360.5±121.6)ng/L (F= 18. 61, P<0. 01). Liver Caspase-3,8,9, 12 activity in 24 hours treatment group was significantly higher than in the control group (F= 84.96, P<0.01). The mRNA expression of iNOS gene, which were not detected in normal controls, reached the peak at 6 hours group after drug treatment and notably dropped in 24 hours and 48 hours groups(F=34.07,P<0.01), p53 gene expression significantly upregulated at 24 hours and 48 hours groups(F=37.43,P<0.01). TNF-α and IL-1β gene expression in the treatment group were higher than in the control group(F=2.94,P<0.05), and both reached the peak at 1 hour treatment group. Conclusions Acute liver failure can be induced by low dose LPS in D-GaiN-sensitized rats. One of the features changes is that Caspase-3,8,9,12 activities are markedly enhanced, and the occurrence of liver injury may be associated with the early high expression of TNF-α, iNOS and p53 gene.

Objective To investigate the effect of acetyl-L-carnitine (ALC) preconditioning on the PC12 cell apoptosis induced by oxygen-glucose deprivation.Methods PC12 cells were seeded in 96-well plates and randomly divided into 5 groups ( n =6 each):control group (group C),cell injury group (group Ⅰ) and preconditioning with different concentrations of ALC groups (groups A1-3 ).In group C,the cells were incubated with DMEM liquid culture medium containing glucose 0.5 g/L for 3 h.In groups Ⅰ and A1-3 the cells were incubated with DMEM liquid culture medium containing sodium hydrosulfite (Na2S2O4) 3 mmol/L and glucose 0.5 g/L for 3 h,and in addition the cells were pre-incubated with ALC 0.2,0.4 and 0.6 mmol/L for 24 h in groups A1-3 respectively.Cell viability was evaluated by MTF assay,while the apoptosis in cells was detected using TUNEL.The activities of ATPase and SOD and MDA content were also detected.Results Oxygen-glucose deprivation significantly increased the number of apoptotic cells and the content of MDA,and decreased the cell viability and activities of SOD and ATPase in group Ⅰ compared with group C ( P ＜ 0.05).Preconditioning with ALC significantly increased the cell viability and the activities of SOD and ATPaes,and decreased the number of apoptotic cells and the content of MDA in groups A1-3 compared with group Ⅰ ( P ＜ 0.05).Conclusion ALC preconditioning can attenuate PC12 cell injury induced by oxygen-glucose deprivation through inhibition of apoptosis in cells.