OBJECTIVETo observe the effect of D-galactosamine (D-GaIN) and lipopolysaccharide (LPS) on liver tissue regeneration and repair in mice following liver injury induced by partial hepatectomy.

METHODSA total of 40 male BALB/c mice were randomly assigned into 2 equal groups to receive intraperitoneal injections of D-GaIN (500 mg/kg) plus LPS (50 µg/kg, given 1 h later) or two doses of saline 24 h prior to 1/3 hepatectomy. The liver weight/body weight (LW/BW) ratio and liver regeneration rate were observed at different time points after partial hepatectomy. Liver cell injury was assessed using HE staining, hepatocyte proliferation evaluated with BrdU staining, and the oval cell proliferation observed with immunohistochemistry.

RESULTSIn mice receiving saline injection, the liver volume was nearly restored 9 days after partial hepatectomy, while in mice with D-GaIN and LPS injections, the liver failed to recover the normal volume even at 14 days, showing a significant difference in the liver regeneration rate between them [(22.6∓105.93)% vs (9.49∓32.55)%, P<0.001]. Significant degenerative changes of the hepatic cells were found in D-GaIN/LPS-treated group, while only mild inflammatory reaction was observed in saline-treated group after partial hepatectomy. Obvious hepatocyte proliferation was observed at day 7 in saline-treated group but not in D-GaIN/LPS-treated group. Oval cell proliferation in the portal area occurred 3 days after partial hepatectomy in D-GaIN/LPS-treated group.

CONCLUSIOND-GaIN and LPS can obviously inhibit hepatocyte regeneration after liver injury in mice. D-GaIN and LPS combined with partial hepatectomy can induce oval cell proliferation.

Animals ; Cell Proliferation ; drug effects ; Galactosamine ; pharmacology ; Hepatectomy ; methods ; Lipopolysaccharides ; pharmacology ; Liver ; cytology ; injuries ; physiopathology ; Liver Regeneration ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Stem Cells ; cytology

c-Jun N-terminal kinase (JNK) is activated during hepatic reperfusion, and JNK inhibitors are known to protect other major organs from ischemia-reperfusion (I/R) injury. We attempted to determine the effect of SP600125, a JNK inhibitor, on hepatic I/R injury using a partial ischemia model in mice. Compared to a vehicle-treated group, the SP600125-treated group showed a greater increase in serum ALT levels 24 h after reperfusion with more severe parenchymal destruction and leukocyte infiltration. Similarly, tissue myeloperoxidase and malondialdehyde levels were higher in the SP600125-treated group, and chemokine expression was also higher in the SP600125-treated group. These data, which are contradictory to previous results, indicate that JNK inhibition by SP600125 may be harmful in hepatic I/R injury. Therefore, care must be taken when investigating the therapeutic use of JNK inhibitors in hepatic I/R injury, especially in the context of the effects of JNK inhibition on inflammatory infiltration.
Reperfusion Injury/*drug therapy ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Mice ; Matrix Metalloproteinase 9/metabolism ; Male ; MAP Kinase Kinase 4/*antagonists & inhibitors ; Liver/cytology/*drug effects/*injuries ; Chemokines/metabolism ; Anthracenes/*pharmacology ; Animals

OBJECTIVETo explore the effects of Ronggan Mixture (RGM) on cell apoptosis by observing the expressions of apoptosis-related genes (Fasl and Bcl-2) in transgenic mice with chronic liver immune injury induced by concanavalin A (ConA).

METHODSSeventy-four transgenic mice were divided into 6 groups, the model group, the normal group, and the treated groups treated respectively with biphenyldicarboxylate (DDB), oriental wormwood (OWW), Yinchenhao Decoction (YCHD) and RGM. Pathologic changes of liver tissue were observed by light microscopy, number of apoptotic cells were determined by TUNEL method, and expressions of apoptosis-related genes, Fasl and Bcl-2, in hepatic T lymphocyte were detected by flow cytometer.

RESULTSEvident pathological changes of liver appeared in the model mice, showed severely destroyed structure of hepatic lobules. As compared with the model group, the changes of liver fibrosis and cell necrosis were much lessened in the RGM group and the YCHD group (P < 0.05). The protein expression of apoptotic gene Fasl and the apoptotic index in the model group were higher than those in the normal group (P < 0.05), but that of the apoptotic inhibiting gene, Bcl-2, in model mice was similar to that in normal mice. As compared with the model group, apoptosis index decreased (P < 0.01), levels of Fasl expression was lower and Bcl-2 expression was higher in the RGM group and the YCHD group (P < 0.05, P < 0.01), and the effect of the two was similar, but significantly superior to that of OWW and DDB (P < 0.05 or P < 0.01).

CONCLUSIONThe Chinese compound, RGM and YCHD can not only relieve the hepatic pathological injury, but also reduce the cell apoptosis in chronic liver immune injury mice through regulating the expressions of Fasl and Bcl-2.

Animals ; Apoptosis ; drug effects ; Concanavalin A ; adverse effects ; immunology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Fas Ligand Protein ; genetics ; metabolism ; Female ; Gene Expression ; drug effects ; Liver ; cytology ; drug effects ; immunology ; injuries ; Liver Diseases ; drug therapy ; genetics ; immunology ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Random Allocation