Spironolactone inhibits hepatic sinusoid angiogenesis in rats with hepatic fibrosis / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of spironolactone against hepatic sinusoid angiogenesis in rats with hepatic fibrosis.</p><p><b>METHODS</b>Twenty-four male Wistar rats were randomly divided into sham-operated group, bile duct ligation (BDL) group, and BDL+SP group in which the rats received daily spironolactone injection (20 mg/kg) the day after BDL. Four weeks after the operation, the rats were sacrificed for examination of liver histology using Masson staining and the expression of vascular endothelial growth factor A (VEGF-A) mRNA in the liver using real-time quantitative PCR. Immunohistochemistry was used to detect the expression of von Willebrand factor (vWF) in the hepatic tissues.</p><p><b>RESULTS</b>Spironolactone significantly inhibited liver fibrogenesis in rats after BDL (METAVIR liver fibrosis scores 2.84∓0.44 vs 19.73∓3.54, P=0.00). Real-time PCR and immunohistochemistry showed that compared with BDL group, spironolactone treatment significantly inhibited the expression of VEGF-A mRNA (0.71∓0.12 vs 1.75∓0.15, P=0.00) and vWF (1.15∓0.09 vs 3.08∓0.17, P=0.00) in the liver. The expression of VEGF-A mRNA was highly correlated with the expression of vWF (r=0.890, P=0.000).</p><p><b>CONCLUSION</b>Spironolactone can inhibit hepatic sinusoid angiogenesis in rats with BDL-induced hepatic fibrosis by inhibiting the expression of VEGF-A.</p>