Expression of activins, follistatin mRNA in the development of hepatic fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To examine the expression changes of activin beta A, beta C, beta E and follistatin mRNA in the development of rat hepatic fibrosis induced by carbon tetrachloride (CCl(4)).</p><p><b>METHODS</b>Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. After carbon tetrachloride injection of 1, 2, 3, 4, 5, 6, and 7 weeks, the 6-12 rats were killed every time. The kinetics of activin beta A, beta C, beta E and follistatin mRNA expression were assessed by the semi-quantity RT-PCR.</p><p><b>RESULTS</b>Activin beta A, beta C, beta E and follistatin mRNA could be detected in normal rat livers. After CCl(4) injection for 2 or 3 weeks, beta A mRNA was transiently decreased and became undetectable, then increased gradually. After CCl injection for 6 and 7 weeks, beta A mRNA level was significantly higher than controls (P<0.01). beta C mRNA could be detected after CCl(4) injection for 1 to 4 weeks and was significantly increased after 5 weeks over controls (P<0.05). beta E mRNA could not be detected after CCl(4) injection for 1 to 5 weeks, but significantly increased after CCl(4) injection for 6 or 7 weeks compared with controls (P<0.01). Except for normal rat liver, no follistatin mRNA was detected in rats after CCl(4) injection.</p><p><b>CONCLUSIONS</b>Activins and follistatin have different expression changes in the development of hepatic fibrosis and the imbalance of activins and follistatin expression may involve in the formation of hepatic fibrosis.</p>

Negative regulatory effects of somatostatin and its analogue on the extracellular matrixes metabolism in hepatic stellate cells / 中国病理生理杂志

AIM:To evaluate the negative regulatory effects of somatostatin(SST) and octreotide(OCT) on the extracellular matrixes(ECM) metabolism in rat hepatic stellate cells(HSCs).METHODS:HSCs were treated with different concentrations of SST or OCT.The mRNA levels of collage type I,III and the intracellular expression of collagen,matrix metalloproteinase-1(MMP-1),tissue inhibitor of metalloproteinase-1(TIMP-1) in activated HSCs were assessed by in situ hybridization(ISH),[3H]-proline incorporation and immunocytochemistry,respectively.In addition,levels of hyaluronic acid(HA),laminin(LM),and procollagen type III(PCIII) in the culture supernatant of HSCs were also detected by enzyme-linked immunosorbent assay.RESULTS:Both SST(10-7 mol/L-10-6 mol/L) and OCT(10-7 mol/L-10-5 mol/L) markedly down-regulated the transcription of collagen type I,III,and the production of collagen,HA,LM,PCIII in HSCs in a dose-dependent manner.Furthermore,HSCs treated with SST(10-6 mol/L) and OCT(10-6 mol/L-10-5 mol/L) significantly reduced TIMP-1 level,which resulted in an elevated ratio of MMP-1/TIMP-1.CONCLUSION:SST and its analogy inhibit the synthesis of ECM and enhance its degradation both at transcriptional and translational levels.

Protective effects of somatostatin and octreotide on hepatocytes / 中国病理生理杂志

AIM:To investigate the protective effect of somatostatin (SST) and octreotide (OCT) on rat hepatocytes. METHODS: The primary hepatocytes were pretreated with different concentrations of SST and OCT. The levels of alanine minotransferase (ALT) and aspartate aminotransferase (AST) in culture supernatant were analyzed by the model of ethanol/carbon tetrachloride (CCl4)-induced hepatocyte injury. Additionally, 75 Sprague-Dawley rats were divided into 5 groups at random, including normal control, model control, SST-treated model groups at high, medium and low doses (200 ?g?kg-1?d-1, 100 ?g?kg-1?d-1 and 50 ?g?kg-1?d-1, respectively). Except for the normal controls, all rats were injected with 40% CCl4 subcutaneously for 8 weeks to establish hepatic fibrosis. Meanwhile, rats of SST-treated model groups were given at different doses of SST twice a day in the same way. Thereafter, the liver function and apoptosis index of hepatocytes were detected by standard enzyme method, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), respectively. RESULTS: Compared with those of injury model group, the hepatocytes pretreated with SST (10-8-10-6 mol/L) and OCT (10-7-10-5 mol/L) exhibited significantly decreased levels of ALT and AST in the culture supernatant. Furthermore, most indices of liver function including ALT, AST, alkaline phosphatase (ALP), total bilirubin (TBIL) and albumin (ALB) improved obviously in all SST-treated groups, especially in the group treated with low dose of SST. The apoptosis index of hepatocytes in the fibrotic liver was also reduced greatly by the treatment with low dose of SST. CONCLUSION: SST and OCT may protect hepatocytes against CCl4-induced injury, inhibit hepatocyte apoptosis, and improve the liver function. These findings suggest them a potential efficiency in the prevention of hepatic fibrosis.