Reason for the particular sensitivity of rats' ocular tissues to endotoxin / 国际眼科杂志(Guoji Yanke Zazhi)

@#Endotoxin-induced uveitis(EIU)has been established as a common model of a special kind of human uveitis, which has been linked to the infection of Gram-negative bacilli. Despite the florid ocular inflammation, there are no significant histopathological abnormalities in other organs or tissues of rats during EIU induced by systemic injection of endotoxin. The phenomenon that rats' ocular tissues are electively affected by endotoxin may reveal some unknown particular sensitivity of rat's ocular tissues. This article would review published papers on the reason for the particular sensitivity of rats' ocular tissues to endotoxin, which might help to provide new ideas for clinical treatment of human uveitis.

Establishment of rat model of retinal branch vein occlusion by photochemical method and correlational research / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the natural course and adverse event of branch retinal vein occlusion (BRVO) rat model induced by laser photochemical method. METHODS: Thirty SD (Sprague Dawley) rats were administrated Bangladesh via tail vein. Then 532nm laser (80mW, 100μ m and 100ms) was performed on retinal vein secondary bifurcation of bitamporal optic disk for 50 spots. Electroretinogram (ERG), fundus fluorescein angiography ( FFA), optical coherence tomography (OCT) and fundus (fluorescein) photograph were applied on 1, 3, 5, 7, 10, 14 and 21d after BRVO model constructed. Two rats were sacrificed, respectively, on 1, 5 and 21d after photocoagulation to carry on HE (Hematoxylin - Eosin stain) and VEGF - α (vascular endothelial growth factor - α) immumohistochemical staining. RESULTS: There were three rats died, three rats with severe retinal detachment for excessive bleeding,one rat with retinal sunken, and one rat with cataract. FFA and fundus ( fluorescein) photograph showed that the successful BRVO rat model was 73% (22/30). It was found that the near-end photocoagulation vein became coarse, far - end became diminution on 1d and the photocoagulation vein total recanalization was on 3-7d. ERG showed the amplification of b wave (dark -adaptation 3.0 response) decreased to 0.694士0.042 of control eyes and on 5-7d decreased to rock bottom about 0.487士0.064 of control eyes. Then it increased Aii the time to 0.708士0.0465 of control eyes on 21d. OCT and HE staining found that retinal ganglion cells and outer nuclear layer became edema on 1d in vivo and in vitro.It was observed that the thickness of retina on photocoagulation vein (0μ m or 250μ m) decreased from 5d and there were 3-4 layer cells in ONL on 21d. The expression of VEGF-α at injured site were significantly more than control eyes on 1d and there were no significant difference on 5d;But the expression of VEGF-α were slightly less than control eyes on 21d. CONCLUSION: Photochemical method was a feasible method to establish BRVO rat model. The evolution and development of the BRVO model could partly mimic human BRVO phenomenon. At the same time, it should be improved to increase the successful model rate.

γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ / 华中科技大学学报（医学）（英德文版）

The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.

γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ / 华中科技大学学报（医学）（英德文版）

The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated.In this study,we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3).The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice.The survival days of mice,and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined.The proportions ofγδ T cells in blood,spleen and liver,and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry.The function of hepatic γδ T cells was examined by cytotoxicity assay.Balb/cJ mice died in 3 to 6 days post MHV-3 infection,with severe hepatic necrosis and significant augmentation of serum ALT and AST levels.The proportions of γδ T ceils in blood,spleen and liver were significantly increased post MHV-3 infection,while those of the early activating molecule CD69-expressing γδ T cells and productions of cytokines tumor necrosis factor-alpha (TNF-α) and interferon-γ (IFN-γ) increased remarkably in the liver.These highly activated liver γδ T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver γδ T cells against hepatocytes might involve the TNF-α and IFN-γ pathway.These results demonstrated that γδ T cells might contribute to the pathogenesis ofMHV-3-induced FVH through the effector cytokines TNF-α and IFN-γ.

SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF / 华中科技大学学报（医学）（英德文版）

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.

SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF / 华中科技大学学报（医学）（英德文版）

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.

KCTD9, a novel potassium channel related gene, was highly expressed in hepatic NK cells and T cells of fulminant hepatitis mice induced by MHV-3 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of a novel potassium channel gene named KCTD9 (potassium channel tetramerization domain containing 9) in model of fulminant viral hepatitis induced by murine hepatitis virus 3 (MHV-3).</p><p><b>METHODS</b>78 BALB/cJ mice(6 male) were randomly and equally assigned to two groups, model group of fulminant viral hepatitis induced by MHV3 and its control. 75 C3H/HeJ female mice were done into two groups, 39 for model group of chronic hepatitis induced by MHV3, 36 for control. Various samples including spleen, liver and lymphocytes from mice of two model groups and the controls were examined for KCTD9 expression by real time quantitative PCR and Immunohistochemistry. Independent-samples T test or one-way ANOVA were carried out in different groups.</p><p><b>RESULTS</b>Increased expressions of KCTD9 mRNA was observed in livers of both model mice of fulminant viral hepatitis and chronic hepatitis. Compared with the control mice, the expressions of KCTD9 mRNA were up-regulated by 577.1-, 8.8-, 59.4- and 10.8-fold in hepatic NK cells, CD4+ T cells, CD8+ T cells and splenic NK cells respectively in model mice of fulminant viral hepatitis 48 hr post MHV-3 infection, whereas down-regulation by 43% and 69% in splenic CD4 + T cells and CD8+ T cells were found respectively. In contrast, in model mice of chronic viral hepatitis the expressions of KCTD9 mRNA were down-regulated by 71% and 51% in hepatic CD4+ T cells and NK cells, respectively. The expression of KCTD9 protein was mainly evidenced in infiltrative mononuclear cells of liver as shown by immunohistochemistry. Basal expression was also investigated and showed constitutive expression of KCTD9 in brain, thymus and other organs in BALB/cJ mice.</p><p><b>CONCLUSION</b>A novel potassium channel gene KCTD9 was highly expressed in hepatic NK cells and T cells of fulminant hepatitis mice induced by MHV-3.</p>

Establishment of pig acute liver failure model and the role of pig fibrinogen-like protein 2 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish a pig model of fulminant hepatic failure for evaluating the pre-clinical efficacy of drug treatment on severe hepatitis, and to detect the expression of fibrinogen-like protein-2 (fgl2) prothrombinase in the model, so as to provide basis for gene therapy targeting to fgl2 for fulminant hepatic failure.</p><p><b>METHOD</b>D-galactosamine hydrochloride was used to induce pig model of fulminant hepatic failure, and the experiment animals were divided into model group (rapid injection of D-galactosamine hydrochloride by ear vein, a dose of 1.2 g/kg) and negative control group (5% Glucose). Clinical, biochemical and pathological changes of animals were observed. The expression of pigs fgl2 (pfgl2) mRNA in liver tissue was detected by real time RT-PCR, the expression of pfgl2 protein in liver tissue was detected by immunohistochemistry.</p><p><b>RESULTS</b>A pig model of fulminant hepatic failure was successfully established using the D-galactose hydrochloride; Real time RT-PCR of liver fgl2 mRNA showed that fgl2 mRNA expression was increased significantly in liver tissue of fulminant hepatic failure pig model compared with the control group (P = 0.016); Immunohistochemical staining showed that there were fgl2 protein expression in liver tissue of fulminant hepatic failure pig model, mainly in the membrane and cytoplasm of hepatocytes, inflammatory cells, liver sinusoidal endothelial cells and vascular endothelial cells of liver cell necrosis region. However, there are no fgl2 positive staining on negative control.</p><p><b>CONCLUSIONS</b>The pig model of fulminant hepatic failure induced by D-galactosamine hydrochloride is similar to human pathological process and can be used to evaluate the pre-clinical efficacy and safety of drug treatment on fulminant hepatic failure. Abnormal expression of pfgl2 at both mRNA level and protein level in the liver of fulminant hepatic failure pig model shows that pfgl2 induced coagulation pathway is also involved in the development of fulminant hepatic failure. Gene therapy targeting fgl2 genes for fulminant hepatic failure may provide a new means for the treatment of fulminant hepatic failure.</p>

Role of CD4-CD8- T cells in the murine hepatitis virus type 3 induced chronic viral hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate role of CD4-CD8- T cells in murine hepatitis virus type 3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice and to identify their surface markers.</p><p><b>METHODS</b>Thirty C3H/Hej mice received 10 Pfu MHV-3 intraperitoneally, the CD4-CD8- T cells were isolated using magnetic bead sorting on 0, 4, 15, 30, 40 days post MHV-3 infection. The cytotoxic effects of CD4-CD8- T cells on normal and infected hepatocytes, CD8+ T cells and unrelated-virus (murine cytomegalovirus, MCMV) infected CD8+ T cells were examined by non-radioactive cytotoxicity assay. The surface markers of CD4-CD8- T cells were determined by flow cytometry.</p><p><b>RESULTS</b>MHV-3 infected CD4-CD8- T cells showed significant cytotoxic effect on CD8+ T cells, but not on infected hepatocytes or MCMV infected CD8+ T cells. The analysis of cell surface markers demonstrated that the CD4-CD8- T cells are a completely new T cell subset.</p><p><b>CONCLUSIONS</b>CD4-CD8- T cells have significant cytotoxic effect on virus specific CD8+ T cells in MHV-3 infected C3H/Hej mice, which suggests that CD4-CD8- T cells have immune modulatory functions in the development of chronic viral hepatitis. The phenotype of these CD4-CD8- T cells detected by flow cytometry is TCR alpha beta +CD3+CD4- CD8- CD25- CD28- CD30- CD44+.</p>

The functions of liver natural killer cells in murine fulminant hepatitis induced by murine hepatitis virus strain 3 / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the role of liver natural killer cells (NK cells) in murine hepatitis virus strain 3 (MHV-3) induced murine fulminant hepatitis.</p><p><b>METHOD</b>Balb/cJ mice (6-8 weeks, female) were intraperitoneally injected with 100 PFU MHV-3. The numbers of NK cells in their livers, spleens, blood and bone marrow and the expression of CD69 on liver NK cells at 0, 24, 48 and 70 h after MHV-3 infection were analyzed by flow cytometry. The cytotoxic activity of liver NK cells was detected by a non-radioactive cytotoxicity assay. The levels of IFN gamma produced by hepatic NK cells were detected by intracellular cytokine staining.</p><p><b>RESULT</b>Following MHV-3 infection, the proportion of liver NK cells in the mice increased remarkably and reached the peak (43.9%+/-2.3%) at 48 h, then kept a high proportion until the mice were sacrificed. The proportion of NK cells in the peripheral blood also significantly increased and reached the peak (18.0%+/-5.4%) at 48 h. However, there were few NK cells in the peripheral blood at 70 h after infection; the ratio was only 1.3%+/-0.6%. In the spleens and bone marrow, the proportions of NK cells were both significantly decreased from 0 h to 48 h and then slightly increased. The expression of CD69 on liver NK cells was highly up-regulated after the infection and the cytotoxic activity of hepatic NK cells at 48 h was also significantly enhanced. In addition, an increase in IFN gamma production by hepatic NK cells was observed at 48 h.</p><p><b>CONCLUSION</b>After MHV-3 infection, NK cells were recruited to the liver quickly, probably from the spleen and bone marrow. Recruited NK cells remarkably express CD69, enhance cytotoxic activity and IFN gamma production, which correlate with the disease severity of fulminant viral hepatitis. Our results suggest that liver NK cells may play a pivotal role in the pathogenesis of fulminant viral hepatitis.</p>

A Primary Study of the Subgroups of T Lymphocytes in MHV-3 Induced Chronic Viral Hepatitis / 中国病毒学

To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units (PFU) of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+CD4-CD25+ T lymphocyte of total T lymphocytes in blood, spleen and liver were examined at 0, 2, 4, 6,8, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection by flow cytosorting. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice, and CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD25- and CD3+CD4-CD25+ T cell ratios decreased accordingly. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.

Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model / 中国病毒学

To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

Construction of the p-mfgl2shRNA and its effect on mfgl2 expression in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct the siRNA plasmid for mfgl2 gene, which has been reported to be involved in a variety of disease developments including fulminant viral hepatitis, acute rejection of allo/zero transplantation and fetal loss syndrome, and to investigate its inhibitory effects on mfgl2 expression in vitro.</p><p><b>METHODS</b>A plasmid p-mfgl2shRNA complimentary to the sequence responsible for the functional domain of mouse fgl2 (mfgl2) was constructed. The pcDNA3.1 mfgl2 expression construct was able to show a satisfactory fgl2 protein expression. The plasmid expression pEGFP and a construct expressing irrelevant shRNA with a random combination of the p-mfgl2shRNA sequence were used as controls. A pEGFP-mfgl2 expressing mfgl2-EGFP fusion protein was also constructed for screening of the effect of p-mfgl2shRNA on the mfgl2 expression.</p><p><b>RESULTS</b>Cotransfection of p-mfgl2shRNA with pEGFP-mfgl2 decreased green fluorescent cells and the lightness of fluorescence within the cells at the 24 h, 48 h and 72 h post-transfection when compared with that in the control groups which were solely transfected with pEGFP-mfgl2. Furthermore the mfgl2 expression was significantly reduced when the pcDNA3.1 mfgl2 expression construct was cotransfected with p-mfgl2shRNA both at mRNA level by RT-PCR and protein level by RT-PCR, immunohistochemistry staining and FACS in both CHO cell and Hela cell lines.</p><p><b>CONCLUSIONS</b>The study demonstrated that the construct of p-mfgl2shRNA successfully interfered in the mfgl2 expression in vitro. It provides a basis for a further investigation of effect in vivo.</p>

Hfgl2/fibroleukin expression in liver and peripheral blood mononuclear cells (PBMC) and its correlation with disease severity / 中华肝脏病杂志

<p><b>OBJECTIVE</b>Viral hepatitis remains a major public health problem and the most common type of liver disease worldwide. There are an increasing number of patients with chronic hepatitis B who develop acute hepatitis on chronic condition (AOC) and die of acute hepatic failure both as a result of lack of understanding of the pathogenesis of the disease and lack of effective treatment. The hallmark of AOC is the extreme rapidity of the necromicroinflammatory process resulting in widespread or total hepatocellular necrosis in weeks or even days. Our previous studies have shown in an experimental animal model of fulminant viral hepatitis caused by murine hepatitis virus strain 3, the importance of macrophage activation, and expression of a unique gene mfgl 2 which encodes a serine protease capable of directly cleaving prothrombin to thrombin, resulting in widespread fibrin deposition within the liver and hepatocyte necrosis. The undergoing study in this report is designed to identify the role of hfgl 2 (human fibrinogen like protein 2) /fibroleukin in patients with viral hepatitis.</p><p><b>METHODS</b>Liver tissues were obtained from 23 patients with AOC hepatitis B, and from 13 patients with inactive chronic hepatitis B (CHB) and 14 patients with chronic hepatitis B with cirrhosis during the year of 1995 to the end of 2001. Liver biopsies were performed within 30 min after the patients were diagnosed with death as a result of acute hepatic failure. Liver samples were also obtained from 4 liver donors as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with AOC hepatitis B and 10 patients with CHB during the May of 2001 to March of 2002 and 10 healthy volunteer as negative control. PBMCs were freshly isolated and smeared on slides and kept at -80 degree C for further use. Histological sections were stained with hemotoxylin and eosin. A 169 bp of hfgl 2 cDNA probe and a polyclonal or monoclonal antibody against hfgl 2 were used to detect the expression of hfgl 2 mRNA and protein in liver samples as well as PBMC by immune histochemistry separately.</p><p><b>RESULTS</b>Liver tissues from the patients with acute on chronic hepatitis had classical pathological features of acute necroinflammation. Hfgl 2 was detected by immune histochemistry in 21 of 23 patients (91.3%) in liver sections from patients with acute on CHB, while only 1 of 13 patients (7.7%) with CHB and cirrhosis and no evidence of active disease had hfgl 2 mRNA or protein expression. 28 of 30 patients (93.3%) with acute on CHB and 1 of 10 with CHB were detected with hfgl 2 expression in PBMC. There was no hfgl 2 expression in either the liver tissue or the PBMC from the normal donors. There was positive correlation of hfgl 2 expression and the severity of the disease displayed by the value of bilirubin and PT.</p><p><b>CONCLUSION</b>The molecular and cellular results reported here in patients with acute on chronic hepatitis and who died of acute hepatic failure correlates with previous report in 8 patients with fulminant hepatic failure (FHF) and mimic closely the changes observed in the murine model of fulminant viral hepatitis in which the pathogenesis of the disease has been studied in a stepwise fashion. This study further suggests that virus induced hfgl 2 prothrombinase/fibroleukin expression and the potent function of the protein it encodes plays a pivotal role in initiating acute severe hepatitis on the baseline of chronic hepatitis. The measurement of hfgl 2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of disease in patients with the AOC hepatitis B and a target for therapeutic intervention.</p>

Liver impairment in murine hepatitis virus 3 induced murine severe acute respiratory syndrome model / 中华传染病杂志

Objectives To investigate dynamic pathological features and virus distribution in the liver with a murine severe acute respiratory syndrome(SARS)model injected with murine hepati- tis virus 3(MHV-3)through trachea.As a representative of host genes,mouse fgl2(mfgl2)pro- thrombinase gene expression and its clinical significance were discussed in SARS associated liver dam- ages.Methods The Balb/cJ mice were infected with 100 PFU of MHV-3 through trachea and Balb/ cJ mice injected with saline were served as control.Survival rate,pathological features in organs and liver function were observed.Virus titers in different organs were determined on monolayer of L2 cells by a standard plaque assay.Virus distribution and cellular localization were studied by in situ hy- bridization.Both mfgl2 and fibrin expressions were examined in the liver by in situ hybridization and immunohistochemistry to investigate the role of mfgl2 in the liver impairment.Results Mice infected with MHV-3 through trachea developed multiple organs damages and died within 5 days,while all mice in control group survived with no histopathological changes.Infected liver tissues showed wide- spread cloudy swelling,prominent ballooning degeneration with mild lymphocytic infiltration in the portal area.Dot and zonal hepatocellular necrosis could be found occasionally.The lungs showed typi- cal interstitial pneumonia and hyaline membranes formation.Other histological changes also could be found in other organs examined.MHV-3 virus replication was identified in all organs observed.The liver function was injured,mfgl2 expression were evidenced mainly in the necrosis areas with fibrin deposition around the necrosis areas.Conclusions Pathological changes of the liver in this murine SARS model can mimic the liver impairment characteristics of SARS in human.In addition to the physical damage induced by the virus,the up-regulation of novel gene mfgl2 in the liver in association with fibrin deposition may play a vital role in the development of SARS associated liver damages.