ABSTRACT
<p><b>OBJECTIVE</b>To investigate the dynamic changes of a-AR, b1-AR and b2-AR expression in hepatic fibrosis.</p><p><b>METHODS</b>Rat hepatic fibrosis model was established by bile duct ligation (BDL). HE and Masson staining were used to determine hepatic fibrosis levels. Immunohistochemistry was applied to detect alpha -smooth muscle actin (alpha -SMA), a marker of hepatic stellate cell (HSC) activation; Western blot and real-time RT-PCR were used to measure the dynamic changes of alpha -AR, beta(1)-AR, beta(2)-AR expression on protein and mRNA levels, respectively, during the development of hepatic fibrosis.</p><p><b>RESULTS</b>(1) HE and Masson trichrome staining showed that the liver fibrosis models were established successfully. (2) At 1, 2, 3, 4 wk after BDL, alpha -SMA positive area density of the model group (10.58% +/- 1.75%, 24.14% +/- 2.02%, 29.74% +/- 2.59%, 34.28% +/- 2.01%) was significantly higher than that of the sham operation group (4.12% +/- 1.51%), P less than 0.01. (3) The expression of alpha -AR, beta(1)-AR, beta(2)-AR protein and mRNA was increased with the development of the hepatic fibrosis (P less than 0.05). (4) alpha -SMA expression was positively associated with alpha -AR, beta(1)-AR, beta(2)-AR, r values were 0.564, 0.753 and 0.606, respectively.</p><p><b>CONCLUSION</b>The expression of alpha -SMA is increased dramatically during the fibrosis, and is positively associated with the expression of alpha -AR, beta(1)-AR and beta(2)-AR.</p>
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Hepatic Stellate Cells , Metabolism , Pathology , Immunohistochemistry , Liver , Metabolism , Pathology , Liver Cirrhosis, Biliary , Metabolism , Pathology , Liver Cirrhosis, Experimental , Metabolism , Pathology , Polymerase Chain Reaction , RNA, Messenger , Genetics , Metabolism , Random Allocation , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha , Genetics , Metabolism , Receptors, Adrenergic, beta , Genetics , Metabolism , Sympathetic Nervous System , Metabolism , Time FactorsABSTRACT
<p><b>AIM</b>To investigate the effect of IH764-3 on the expression of MMP-13 and TIMP-1 by H2O2-stimulated hepatic stellate cell and the alteration of FAK during this process.</p><p><b>METHODS</b>The expression of MMP-13 and FAK mRNA was examined by RT-PCR. TIMP-1 mRNA was analyzed by in-situ hybridization. FAK and TIMP-1 were evaluated at protein level through Western blotting method.</p><p><b>RESULTS</b>Being incubated for 2 h, compared with control group, MMP-13 mRNA was upregulated by IH764-3, but TIMP-1 transcription was reduced in a dose-dependent manner, accompanied with the decrease of FAK mRNA. The expression of TIMP-1 and FAK protein in HSC also decreased after being exposed by IH764-3 for 24 h.</p><p><b>CONCLUSION</b>IH764-3 can induce the expression of MMP-13 and inhibit the expression of TIMP-1. Down-regulating the expression of FAK mRNA may be one of its mechanisms.</p>