Losartan regulates oxidative stress via caveolin-1 and NOX4 in mice with ventilator- induced lung injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of losartan in regulating oxidative stress and the underlying mechanism in mice with ventilator-induced lung injury.</p><p><b>METHODS</b>Thirty-six male C57 mice were randomly divided into control group, losartan treatment group, mechanical ventilation model group, and ventilation plus losartan treatment group. After the corresponding treatments, the lung injuries in each group were examined and the expressions of caveolin-1 and NOX4 in the lung tissues were detected.</p><p><b>RESULTS</b>The mean Smith score of lung injury was significantly higher in mechanical ventilation model group (3.3) than in the control group (0.4), and losartan treatment group (0.3); the mean score was significantly lowered in ventilation plus losartan treatment group (2.3) compared with that in the model group (P<0.05). The expressions of caveolin-1 and NOX4 were significantly higher in the model group than in the control and losartan treatment groups (P<0.05) but was obviously lowered after losartan treatment (P<0.05). Co-expression of caveolin-1 and NOX4 in the lungs was observed in the model group, and was significantly decreased after losartan treatment.</p><p><b>CONCLUSION</b>Losartan can alleviate ventilator-induced lung injury in mice and inhibit the expression of caveolin-1 and NOX4 and their interaction in the lungs.</p>

Prolonged angiotensin-(1-7) infusion inhibits hepatic fibrosis in rats with bile duct ligation / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the inhibitory effect of angiotensin-(1-7) on liver fibrosis induced by bile duct ligation in rats.</p><p><b>METHODS</b>Eighteen Wistar rats were randomized into 3 groups and subject to sham operation, bile duct ligation (BDL), or BDL with angiotensin-(1-7) treatment. An osmotic minipump was implanted intraperitoneally for administration of saline in the sham-operated and BDL groups and angiotensin-(1-7) (25 µg·kg(-1)·h(-1)) in angiotensin-(1-7) treatment group. After a 4-week treatments, the fibrosis score, Masson staining, and hydroxyproline assay were used to evaluate the level of liver fibrosis in the rats, and immunohistochemistry was used to detect expression of α-smooth muscle actin (α-SMA) in the liver tissue.</p><p><b>RESULTS</b>Compared with BDL group, a 4-week treatment with angiotensin-(1-7) following BDL significantly reduced the fibrosis score (2.33±0.52 vs 5.17±0.75), hydroxyproline content (0.36±0.03 vs 0.52±0.04) and α-SMA expression (54.11±17.55 vs 191.84±31.72) in the liver tissue of the rats (P<0.01).</p><p><b>CONCLUSION</b>Prolonged infusion of angiotensin-(1-7) inhibit the formation of hepatic fibrosis in rats following bile duct ligation.</p>

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

<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>