The effect of resistin on nuclear factor-kB and tumor necrosis factor-a expression in hepatic steatosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the potential regulatory role played by the hormone resistin in lipid metabolism and expression of nuclear factor (NF)-kB and tumor necrosis factor (TNF)-a during hepatic steatosis.</p><p><b>METHODS</b>A non-alcoholic fatty liver disease (NAFLD) cell model was established by treating the normal human hepatic cell line, L02, with palmitic acid. Four research groups of L02 cells were generated: C group (control, no palmitic acid treatment), P group (NAFLD model, treated with 20 microg/ml palmitic acid), CR group (C group treated with 50 microg/L recombinant human resistin), and PR group (P group treated with 50 microg/L recombinant human resistin). All treatments were carried out for 72 hours. Oil red O staining was used to detect the intracellular changes in lipid drops. Biochemical assays were used to measure triglycerides (TGs), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) levels in culture medium. The mRNA and protein expression levels of insulin receptor substrate (IRS)-2, NF-kB, and TNF-a were determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively.</p><p><b>RESULTS</b>The TG, ALT, AST, and GGT levels were higher in the P, CR, and PR groups than in the C group. The NF-kB mRNA level was also higher in the P, CR, and PR groups (Student's t = 17.64, 22.03, 26.06 respectively) than in the C group, as was the TNFa mRNA level ( t = 5.67, 5.38, 11.64), but the IRS-2 mRNA level was lower ( t = 8.19, 9.23, 20.93) (all, P less than 0.05). In addition, no significant difference in these mRNA levels were found between the P group and the CR group (NF-kB: t = 1.75, TNFa: t = 0.58, IRS-2: t = 2.14; all, P more than 0.05). The detected protein levels of NF-kB, TNFa, and IRS-2 were consistent with the mRNA levels.</p><p><b>CONCLUSION</b>Resistin can promote steatosis in LO2 cells through the NF-kB signaling pathway, thereby contributing to the NAFLD pathogenic process.</p>

Clinical significance of histopathologic and ultrastructural pathologic examination in etiological diagnosis of infantile cholestatic diseases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the features of histopathologic and ultrastructural pathologic changes of liver biopsy in patients with infantile cholestatic disease, and to investigate its diagnostic significance combining with the clinical data.</p><p><b>METHODS</b>Thirty-six children diagnosed as infantile cholestatic disease and received liver biopsy in Chongqing Medical University Children's Hospital from Jun 2007 to Oct 2008 were enrolled and the pathologic and ultrastructural pathologic changes of liver were analyzed.</p><p><b>RESULTS</b>Morphologic changes under light microscope in liver tissues included hepatocyte swelling, hepatocyte denaturation, hepatocyte necrosis, multinucleated giant cell formation, bile duct proliferation, fiber tissues proliferation and inflammatory cells infiltration in liver lobules and portal regions. The characteristics of cholestasis including intralobular cholestasis, acinus formation, feather-like cytoplasmic filaments and bile stasis in bile canaliculi were observed. The morphologic changes of biliary atresia were observed in 7 cases whose image investigations showed no obstruction of biliary tract. Nuclear changes, resolution of cytoplasm, inflammatory cell infiltration, collagen fiber proliferation and increased number of lysosomes were observed under electromicroscope. Two cases of glycogen storage disease, 1 case of Niemann-Pick disease and 1 case of lipid storage disease with unknown cause were confirmed by the combination of histological changes and clinical manifestations.</p><p><b>CONCLUSION</b>Common pathologic changes of liver tissues existed under light microscope or electroscope. The diagnosis of hereditary metabolic disorders could be made increasingly by application of these two technologies in clinical practice. It is difficult to diagnose biliary atresia in early childhood by image investigations and the pathological changes of liver tissues are helpful.</p>

The clinicopathological study of infantile cytomegalovirus hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features of infantile cytomegalovirus hepatitis.</p><p><b>METHOD</b>Liver biopsies from 30 cases of infantile cytomegalovirus hepatitis were observed under optical microscope and electronic microscope.</p><p><b>RESULT</b>The main clinical manifestations were jaundice, splenohepatomegaly and hypohepatia. Laboratory test showed dysfunction of liver, high level of CMV DNA, and high titer of anti-CMV antibody. Imaging examination demonstrated hepatomegaly. The histological changes were hepatocellular degeneration, necrosis, apoptosis, and fibrosis. The histological characteristics of cytomegalovirus hepatitis, including intranuclear inclusions in multinucleated giant cells and pseudo-lumens, were also observed under optical microscope. In addition, virion was observed in the nuclei and cytoplasm of hepatocytes under electronic microscope.</p><p><b>CONCLUSION</b>The viral DNA and serological tests have limited utility for the diagnosis of infantile cytomegalovirus hepatitis, and the final diagnosis depends on histopathology.</p>

Effect of tea polyphenols on expression of nuclear factor kappa B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of tea polyphenols (TP) on expression of nuclear factor kappa B (NF-kB) in rats with alcoholic liver diseases and in cells treated with alcohol.</p><p><b>METHODS</b>22 female Wistar rats were randomly divided into three groups: a control group, an alcohol model group and a TP plus alcohol group. All treatments were injected into stomach through intragastric tube. L02 cells were divided into five groups: a control group, an alcohol treated group, a prevention group (cells were treated with TP for 3 days, and then treated with alcohol), an intervention group (cells treated with TP and alcohol), and a therapeutic group (cells were treated with alcohol for 3 days, and then treated with TP). Histopathology was observed under light microscope (LM); serum MDA, ROS in cells were quantified by optical density measurement; the expression of NF-kB and IkB was determined by RT-PCR; and the activity of NF-kB was checked with Electrophoretic Mobility Shift Assay (EMSA).</p><p><b>RESULTS</b>LM indicated hepatocytes were injured obviously in the model group. Serum MDA and cells ROS in TP treated groups were significantly lower than the alcohol treated group. The level of NF-kB mRNA expression in TP treated groups(rats: 0.58+/-0.16, cells: 0.60+/-0.03, 0.59+/-0.01, 0.59+/-0.01) were significantly lower than the alcohol treated group (rats: 1.15+/-0.03, cells: 0.76+/-0.03) (P<0.01), the level of IkB mRNA expression in the prevention group, intervention group, and therapeutic group (0.51+/-0.01, 0.50+/-0.01, 0.50+/-0.12) were significantly higher than the alcohol treated group (0.61+/-0.03) (P<0.05), the difference among the three groups was not significant (P>0.05). The activity of NF-kB in TP treated rats(DNA stain: 669.85+/-41.34, Protein stain: 675.35+/-18.27) was significantly lower than the alcohol treated rats(DNA stain: 1410.78+/-22.19, Protein stain:1426.08+/-33.15) (P<0.01); NF-kB activity in cells of the prevention, intervention, therapeutic groups (DNA stain: 713.07+/-11.91, 710.79+/-14.99, 693.45+/-71.69; Protein stain: 758.88+/-34.65, 753.07+/-76.78, 725.77+/-36.09) was significantly lower than the alcohol treated cells (DNA stain: 849.94+/-12.45, Protein stain: 925.96+/-5.78) (P<0.01), the difference among the three TP treated groups was not significant (P>0.01).</p><p><b>CONCLUSION</b>TP can alleviate and prevent alcohol-induced liver injury via inhibiting NF-kB activation.</p>

Expression of augmenter of liver regeneration in hepatic tumor cells and its clinical significance / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of augmenter of liver regeneration (ALR) on the proliferation of hepatocytes and hepatic tumor cells and the expression of ALR in herpatocellular carcinoma (HCC).</p><p><b>METHODS</b>Primary rat hepatocytes, QGY and HepG2 cells were cultured separately with ALR from different species. Cell proliferation was detected by their 3H-TdR uptake. The expression of ALR was examined in 9 normal hepatic tissues and 21 HCC cases using immunohistochemistry method.</p><p><b>RESULTS</b>Different ALRs could stimulate the proliferation of HepG2 and QGY cells in a dose-dependent way in vitro, but all ALR had no influence in the proliferation of primary rat hepatocytes. The expression of ALR was absent in normal hepatic tissues, but present in all HCC hepatic tissues. However, the expression of ALR had no relationship with the differentiation and size of the carcinomas.</p><p><b>CONCLUSION</b>ALR might play an important role in the occurrence and development of HCC.</p>

A study on the clinical and pathological efficacy of lamivudine in the treatment of chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate clinical effect, liver pathohistological changes (including pathology, HBV markers in liver tissue) in patients with chronic hepatitis B.</p><p><b>METHODS</b>70 patients of chronic hepatitis B were administered 100 mg Lamivudine orally daily for 1 year. The serum HBV-DNA, HBeAg/anti-HBe, hepatic chemistry and the hepatic fibrosis markers were studied. The needle biopsy of liver were performed in 35 patients before and after treatment and Knodell pathological score were done, HBsAg, HBcAg, alpha-SMA in liver tissue were examined by immunohistochemistry method.</p><p><b>RESULTS</b>After 1 year treatment the full response rate, partial response rate and no response rate were 23.72%, 69.49% and 6.78%, the patients in whom HBeAg seroconversion had higher base-line Alanine aminotransferase levels than the patients without seroconversion. Activity index of hepatic histology in 41.18% patients had a significant decrease. Histological assessment revealed that necrosis in portal area, pylenphlebitis and fibrosis were obviously alleviated. The liver immunohistochemistry examination showed HBcAg and alpha-SMA in liver decreased significantly in the patients with HBeAg seroconversion, no obvious alteration was observed in HBsAg expression. Lamivudine seems an effective compound with high safety and low side effect.</p><p><b>CONCLUSION</b>These results suggested that lamivudine (100mg/d) could suppress HBV-DNA replication, promote ALT normalization, accelerate HBeAg/anti-HBe seroconversion, improve the liver pathological changes, slow down the development of liver fibrosis</p>

Effect of Rhein on the development of hepatic fibrosis in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of rhein on the development of hepatic fibrosis.</p><p><b>METHODS</b>The animal models were made with carbon tetrachloride (CCl(4)) mixed with vegetable oil (3/2, v/v), which was injected subcutaneously twice a week for 6 weeks, and with 5% ethanol for free drinking water. At the same time, Rhein was administrated at the dose of 25 mg/kg or 100 mg/kg once a day for 6 weeks. The changes of both biochemical markers, such as the levels of alanine aminotransferase (ALT), hyaluronic acid (HA), procollagen type III (PCIII) in serum and SOD, malondialdehyde (MDA) in liver, and related histopathological parametres were determined.</p><p><b>RESULTS</b>Compared with the model group, there were three kinds of changes in the larger quantity of rhein treated group. (1) The levels of ALT, HA, PCIII in serum and MDA in liver homogenate were decreased significantly (from 150 U/L +/- 16 U/L to 78 U/L +/- 18 U/L, 321 microg/L +/- 97 microg/L to 217 microg/L +/- 75 microg/L, 31 microg/L +/- 14 microg/L to 16 microg/L +/- 6 microg/L and 3.67 nmol/mg +/- 0.68 nmol/mg to 1.88 nmol/mg +/- 0.34 nmol/mg, respectively, t > or 2.977, P<0.01). However the level of SOD in liver was increased (from 62.45 NU/mg +/- 8.74 NU/mg to 91.26 NU/mg +/- 14.04 NU/mg, t=4.453, P<0.01). (2) The expressions of transforming growth factor beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA) in liver were markedly reduced (P<0.05 and P<0.01). (3) The collagen staining positive area was decreased and the grade of fibrosis was reduced significantly in liver (P<0.05 and P<0.01).</p><p><b>CONCLUSION</b>Rhein can protect hepatocyte from injury and prevent the progress of hepatic fibrosis in rats, which may associate with that rhein plays a role in antioxidation, anti-inflammation, inhibiting the expression of TGF-beta1 and suppressing the activation of hepatic stellate cells (HSCs).</p>