No abstract available.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

In acute injury, liver recovers completely without any scarring change or complication. However, large portion of liver is changed into fibrotic state by excessive production of extracellular matrix (ECM) under chronic injury. Excessive production of ECM results in hepatic fibrosis and repeated process of hepatic fibrosis progress into liver cirrhosis. Liver cirrhosis is an irreversible and terminal state of chronic liver disease and one of the major causes of death in Korea. To block the progression to liver cirrhosis, various studies in the field of virology and immunology have been proceeded. Recently, studies on the hepatic fibrogenesis have progressed with the development of molecular biology. Hepatic stellate cells (HSC) play a key role in the pathogenesis of hepatic fibrosis by producing ECM. The degree of hepatic fibrosis depends on the proliferation and activation of HSC and increased net production of collagen. Therefore, inhibition of HSC activation is one of the main ways to block the progression of hepatic fibrosis. Many kinds of factors such as oxidative stress, acetaldehyde, ascorbic acid, transforming growth factor-beta (TGF-beta) and carbon tetrachloride (CCl4) have been reported to activate HSC and stimulate collagen gene expression. Although there are no definite and effective antifibrogenic agents, possible candidates are antioxidants, interferon, retinoids such as beta-carotene, flavonoids, renin-angiotensin system inhibitors and peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists. We tried to evaluate the charateristics of HSC in order to develop agents that inhibit hepatic fibrogenesis.
Extracellular Matrix/*metabolism ; Fibrosis ; Humans ; Liver/blood supply/metabolism/*pathology ; Liver Cirrhosis/etiology/genetics/*metabolism

OBJECTIVETo explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.

METHODSNinety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.

RESULTS12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).

CONCLUSIONVM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Lymphatic Vessels ; Male ; Middle Aged ; Vascular Endothelial Growth Factor C ; metabolism

OBJECTIVETo explore the relationship between the expression of cyclooxygenase-2 (COX-2) and angiogenesis in hepatocellular carcinoma.

METHODSForty Wistar rats were divided into two groups: a model group (30 rats) and a normal group (10 rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN) in the model group rats. The rats were sacrificed in batches at the 6th, 12th and 18th week of the experiment. Histological sections of liver tissues were made using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2 protein in the liver tissues were evaluated using immunohistochemical methods.

RESULTSIn liver sections from the model group there were marked pathological changes (steatosis, cell infiltration, cirrhosis and liver cancer). The expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were remarkably increased during the hepatocellular carcinogenesis. Microvessel density (MVD) was also obviously raised during the process of the cancer development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2 (r=0.858, 0.788, 0.684, respectively; all P less than 0.01). There was also a direct correlation between the COX-2 and VEGF/KDR/MMP-2/MVD (r=0.771, 0.599, 0.690, 0.788, respectively; all P < 0.01).

CONCLUSIONCOX-2 can promote tumor angiogenesis during rat hepatocellular carcinogenesis. This may be one of the mechanisms in which COX-2 promotes carcinomas.

Animals ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Cyclooxygenase 2 ; biosynthesis ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Neovascularization, Pathologic ; Rats ; Rats, Wistar

The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-alpha, MDA and MPO. The levels of TNF-alpha in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.
Intestines/*pathology ; Liver/*blood supply ; Liver/metabolism ; NF-kappa B/*biosynthesis ; Random Allocation ; Rats, Wistar ; Reperfusion Injury/*metabolism

OBJECTIVETo investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion.

METHODSA rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues.

RESULTSRemoving portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P < 0.05), while in lung tissue in group A10 were also markedly reduced (P < 0.05). The activation of SOD in group A5 were significantly increased (P < 0.05).

CONCLUSIONSRemoval of portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.

Animals ; Disease Models, Animal ; Female ; Ischemia ; metabolism ; pathology ; Kidney ; metabolism ; pathology ; Liver ; blood supply ; Lung ; metabolism ; pathology ; Male ; Portal Vein ; pathology ; Rabbits ; Random Allocation ; Reperfusion Injury ; metabolism ; pathology

OBJECTIVETo investigate the effects of ischemic postconditioning on the expression of HO-1 in the liver graft ischemia and reperfusion injury in rats.

METHODSFifty-six male SD rats were randomly divided into four groups: sham-operation group (sham) (n = 8), ischemia and reperfusion group (I/R)(n = 16), ischemic postconditioning group (IPo) (n = 16) and inhibitor of HO-1 group (ZnPP) (n = 16). Donor livers were preserved in 0 - 4 degrees C normal saline, and the period of cold preservation and anhepatic phase were 90 min and 15 min. At 6 h after portal vein reperfusion, blood samples were obtained from the abdominal aorta to determine the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), simultaneously liver tissues were taken to determine the level of malondialdehyde (MDA), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) mRNA. The changes of liver tissues were observed by HE staining and electron microscope.

RESULTSSOD activity was significantly lower whereas MDA content was significantly higher in I/R group than that in Sham group (P < 0.05). The expression of HO-1 in I/R group was higher than that in Sham group (P < 0.05). MDA content was significantly lower whereas SOD activity was significantly higher in IPO group than that in I/R group (P < 0.05), and the expression of HO-1 in IPO group was significantly stronger than that in I/R group (P < 0.05). SOD activity and the expression of HO-1 were significantly lower whereas MDA content was significantly higher in ZnPP group than that in I/R group (P < 0.05). The changes of liver tissues also proved the previous results.

CONCLUSIONSIschemic postconditioning attenuates liver graft injury induced by I/R in rats. The mechanism might be related with the induction of HO-1 and enhancement of liver graft antioxidation.

Animals ; Disease Models, Animal ; Heme Oxygenase (Decyclizing) ; metabolism ; Liver ; blood supply ; metabolism ; pathology ; Liver Transplantation ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology

The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-alpha, MDA and MPO. The levels of TNF-alpha in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.
Animals ; Intestines ; pathology ; Liver ; blood supply ; metabolism ; Male ; NF-kappa B ; biosynthesis ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism

Animals ; Female ; Leupeptins ; therapeutic use ; Liver ; blood supply ; NF-kappa B ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; pathology