AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism. METHODS: Rat hepatic fibrosis was induced by carbon tetrachloride (CCl4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PI, PII) groups. Except for rats in control group, all rats were given subcutaneous injection of 400mL/L CCl4, twice a wk for 8 wk. Rats in PI and PII groups were also treated with pioglitazone of 3mg/kg, daily via gastrogavage beginning on the 1st day and at the end of the 2nd week, administration of CCl4 respectively. Liver functions (ALT, AST), serum fibrotic markers (HA, LN, PCIII) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for a-smooth muscle actin (a-SMA) were performed. Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree. RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST , HA, LN and PCIII (P<0.05 or <0.01). The HP concentrations in PI (210.90

Background/Aims: We have previously demonstrated that human liver Annexin V (hAV), a Ca2+-dependent phospholipid binding protein, binds specifically to small HBsAg (SHBsAg). Because of the propensity of AV to bind phospholipids, we here examine the role of phospholipids, as component of the HBV envelope, in binding to hAV and in HBV infection. Methods: The influence of phospholipids (phosphatidylserine and phosphatidylcholine) on the binding of hAV to SHBsAg or to anti-hAV monoclonals was determined by ELISA. Their influence on HBV infection was investigated using an in vitro HBV infection assay. Results: Two monoclonals, specific against MY were able to block the binding of hAV to SHBsAg and recognized different epitopes of hAV The binding of one of these monoclonals to hAV could be inhibited by phosphatidylserine, but not by phosphatidylcholine. Further experiments revealed that phosphatidylserine could also inhibit the binding of hAV to SHBsAg and could even prevent HBV infection in vitro. Phosphatidylcholine had no effect on the binding of hAV to SHBsAg and could not prevent HBV infection in vitro. However, since phosphatidylserine was not able to abolish the binding of the other blocking monoclonal to hAV, a non-phospholipid component of the HBV envelope must also be involved in hAV binding. Conclusions: These results indicate that phosphatidylserine and a non-phospholipid component of the HBV envelope are involved in hAV binding and in HBV infection.

AIM: The transforming growth factor-beta (TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis. Smad proteins can either positively or negatively regulate TGF-β responses. In this study, the therapeutic effects of Chinese traditional compound decoction, JinSanE, and the changes of TGF-β/Smad signaling pathway system in carbon tetrachloride (CCl4)-induced rat experimental liver fibrosis were examined. METHODS: Seventy-two healthy Wistar rats were assigned to groups including normal control group, CCl4 model group, JinSanE treatment group I and JinSanE treatment group II. Each group contained 18 rats. All groups, except the normal control group, received CCl4 subcutaneous injection for 8 wk. Rats in JinSanE groups I and II were orally treated with JinSanE daily at the 1st and 5th wk, respectively, after exposure to CCl4. The expression of TGF-β1 and TGF-β1 type II receptor (TRII) mRNA in the liver was determined by reverse transcription polymerase chain reaction, and the expression of TGF-β1, Smad3 and Smad7 by immunohistochemistry. The liver histopathology was also examined by HE staining and observed under electron microscope. The activities of several serum fibrosis-associated enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), the levels of serum hyaluronic acid (HA) were assayed. RESULTS: Hepatic fibrosis caused by CCl4 was significantly inhibited in the JinSanE-treated groups. The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group. The expression of TGF-β1, TRII and Smad3 was significantly higher in the model group than that in the JinSanE-treated groups, and the active/total TGF-β1 ratio in the JinSanE groups was suppressed. Expression of TRII mRNA and Smad3 proteins showed a distribution pattern similar to that of TGF-β1 with a direct correlation in terms of the degree of hepatic fibrosis. The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group. The contents of ALT, AST and HA were significantly lower in the JinSanE-treated groups than those in the model group. CONCLUSION: Traditional Chinese medicine, JinSanE, prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1, TRII and Smad3 signal proteins, and increases expression of Smad7 signal protein in vivo.

目的 观察培哚普利和缬沙坦抗大鼠肝纤维化的疗效。方法 60只Wistar大鼠随机平均分为4组：正常组、模型组、培哚普利治疗组和缬沙坦治疗组。四氯化碳诱导大鼠肝纤维化模型，治疗组于造模第4周开始分别予以培哚普利和缬沙坦灌胃。RT-PCR检测肝组织转化生长因子-Ⅱ型受体（TGFR Ⅱ mRNA）；免疫组化技术检测TGF-β1、Smad3及Smad7在肝内的表达及定位，肝组织HE染色检测病理改变。结果 与模型组大鼠比较，经培哚普利或缬沙坦治疗大鼠肝内TGF-β1与TGFR Ⅱ mRNA、以及Smad3蛋白表达明显降低；而Smad7的表达增加。TGF-β1与Smad3的免疫阳性反应信号主要位于纤维间隔中的细胞浆，Smad7则主要在肝细胞浆表达，上述物质在两种药物组之间表达差异无显著性（P>0.05）。培哚普利或缬沙坦治疗后肝小叶均趋于正常，纤维间隔明显变薄。结论 培哚普利或缬沙坦均能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度，其机理可能与直接或间接抑制肝内TGF-β1、与TGFR Ⅱ mRNA及Smad3表达，并促进Smad7表达有关。