CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

Study on Intervenient Effect of Angelica Sinensis Polysaccharide on Immunological Liver Injury and Its Mechanism in Mice

Objective: To study the changes of expressions of nitric oxide synthase (NOS) of the constitutive type (cNOS) and inducible type (iNOS), the apoptosis related genes bax and bcl 2, as well as the tumor necrosis factor (TNF α) in immunological liver injury (ILI) and to explore the preventive effects of Angelica sinensis polysaccharide (ASP) on ILI and its mechanism in mice.Methods: ILI model mice induced by intraperitoneal injection of lipo polysaccharide (LPS) and BCG vaccine were treated with ASP of different doses (30mg/kg, 60mg/kg) by gastrogavage every day for 7 days. The serum alanine transaminase (ALT) and glutathione S transferase (GST) activities and NO content in the liver were detected; the expressions of cNOS, iNOS, bcl 2, bax were assessed with immuno histochemical method, and the TNF α mRNA expression in the liver was observed by reverse transcriptase polymerase chain reaction (RT PCR).Results: Compared with the normal mice , the NO production and ALT, GST levels were raised significantly in the model mice, the TNF α mRNA expression was also raised significantly. But no obvious changes of cNOS was found. Small dose ASP (30mg/kg) could reduce NO production and ALT, GST levels in model mice by 19.5%, 23.7% and 40.0% respectively, decrease the expression of iNOS and bax by 48.3%, and 26.4%, and increase the expression of cNOS, bcl 2 by 66.9% and 337.3%, respectively, but it could not reduce the TNF α mRNA expression in the liver. Large dose of ASP (60mg/kg) was not more effective than that of small dose.Conclusion: Changes of NO production and TNF α mRNA may play an important role in ILI. The mechanism of ASP in intervening ILI may be through modulation on cNOS, iNOS, bax, bcl 2 expression to block the damage of BCG vaccine and LPS on hepatocytes.

Experimental study on the efficacy of Fuganling granula on protecting against immunological hepatic injury

To study the efficacy of Fuganling granula(FGL,复肝灵颗粒)in treating mouse immunological hepatic injury that was caused by Bacille Calmette Guerin(BCG)and lipopolysaccharide(LPS),a total of 60 mice were adopted,among which,50 mice were given intraperitoneal injection with BCG and LPS to establish an immunological liver injury model and then were randomly divided into 5 groups(10 mice/group):4 groups received treatment of FGL orally at the doses of 100 mg/kg(high-dosage),50 mg/kg(middle-dosage),25 mg/kg(low-dosage)and bifendate orally at the dose of 80 mg/kg,respectively.One group was treated with distilled water orally.The remaining 10 mice were given distilled water intraperitoneally as the normal control group.The indices of thymus,liver and spleen,and the activities of the alanine aminotransferase(ALT),aspartate aminotransferase(AST)in the serum were detected.Compared to the normal rat,the model group’s thymus index decreased significantly.The liver index and spleen index increased significantly.The activities of serum ALT and AST increased signifi-cantly(all P<0.01).Compared to the model control group,the group treated with FGL in high-dosage,middle-dosage or low-dosage can decrease the activities of ALT and AST and the group treated with FGL in high-dosage and middle-dosage can increase the thymus index significantly(P<0.01).This experiment established the immunological liver injury model successfully and found that FGL has a remarkably protective effect on this kind of immunological hepatic injury.