Differential gene expression profiles in acute hepatic failure model in mice infected with MHV-3 virus intervened by anti-hepatic failure compound

Abstract

Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure infected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% respectively 48 h after intraperitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oligonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fgl2, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

Keywords

anti-hepatic failure compound / acute hepatic failure / immune related genes / gene expression profiles

References

[1] HuangJ. Q., HuangT. J., ZhangJ. J., et al.. Clinical effect on severe hepatitis treated by compound anti-fulminant hepatitis. Chin J Integr Tradit Western Med Liver Dis (Chinese), 2006, 16(6): 331-333

[2] NingQ., YangD. L., LuoX. P., et al.. Fulminant viral hepatitis: mice model and its clinical implications. Clin J Hepatol (Chinese), 2002, 10(3): 224-226

[3] NingQ., BrownD., ParodoJ., et al.. Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgt2 prothrombinase. J Virol, 1998, 160: 3487-3493

[4] ChomomczyskiP., SacchiN.. Single-step method of RNA isolation by acid guanidinium thiocyanate phenol chloroform extraction. Anal Chem, 1987, 162: 156-159

[5] SchenaM., ShalonD., DavisR. W., et al.. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science, 1995, 270: 467-470

[6] IvakhnoS. S., KorneliukO. I.. Microarrays: technologies overview and data analysis. Ukr Biokhim Zh, 2004, 76(2): 5-19

[7] TsuchiyaN., TokushigeK., YamaguchiN., et al.. Influence of TNF gene polymorphism in patients with acute and fulminant hepatitis. J Gastroenterol, 2004, 39(9): 859-866

[8] KondoY., KobayashiK., AsabeS., et al.. Vigorous response of cytotoxic T lymphocytes associated with systemic activation of CD8 T lymphocytes in fulminant hepatitis B. Liver Int, 2004, 24(6): 561-567

[9] BendallL.. Chemokines and their receptors in disease. Histol Histopathol, 2005, 20(3): 907-926

[10] LiX. J., XiaL. H., HuangJ. Q., et al.. Expression of fgl2 prothrombinase gene in patients with fulminant hepatitis. J Huazhong Univ Sci Technol (Health Sciences) (Chinese), 2003, 32(6): 613-615

[11] ChenY., NingQ., WangB. J., et al.. Expression of human fibroleukin gene acute on chronic hepatitis B and its clinical significance. Natl Med J China (Chinese), 2003, 83(6): 446-450

[12] ZhuF., NingQ., ChenY., et al.. Hfgl 2/fibroleukin expression in liver and peripheral blood mononaclear cells (PBMC) and its correlation with disease severity. Chin J Hepatol (Chinese), 2004, 12(7): 385-388

[13] NingQ., LakatooS., LiuM., et al.. Induction of prothrombinase fgl2 by the nucleocapsid protein of virulent mouse hepatitis virus is dependent on host hepatic nuclear factor-4 alpha. J Biol Chem, 2003, 278(18): 15 541-15 549

[14] BrownS., HeinischI., RossE., et al.. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature, 2002, 418(6894): 200-203

[15] ClarkG. J., FitzpatrickS., KuoB., et al.. CMRF-35A, CMRF-35H: potential new CD. 1. J Biol Regul Homeost Agents, 2002, 16(3): 233-235

[16] ErnstS., ZobiackN., BoeckerK., et al.. Agonist-induced trafficking of the low-affinity formyl peptide receptor FPRL1. Cell Mol Life Sci, 2004, 61(13): 1684-1692

[17] YuntaM., LazoP. A.. Apoptosis protection and survival signal by the CD53 tetraspanin antigen. Oncogene, 2003, 22(8): 1219-1224