Transforming growth factor-β1 regulates renal α3 and β1 integrin expressions in diabetic rats: a new insight into the renoprotective effect of irbesartan / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the association between renal transforming growth factor-β1 (TGF-β1) and the expressions of α3 and β1 integrins and observe the effect of irbesartan on their expressions in diabetic rats.</p><p><b>METHODS</b>Thirty 8-week-old male Wistar rats were randomly divided into normal control group (n=7), diabetic control group (n=14) and irbesartan group (n=9). Rat models of diabetes were established by a single peritoneal injection of streptozotocin (STZ), and 4 weeks later the rats received irbesartan treatment for 8 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to measure the urinary albumin excretion rate, and PAS staining was utilized to observe the renal pathologies. Immunohistochemistry was performed for semi-quantitative determination of podocyte density, and real-time RT-PCR was used to detect the renal TGF-β1 and α3/β1 integrin mRNA expressions.</p><p><b>RESULTS</b>In diabetic rats, the expression of renal TGF-β1 mRNA was significantly increased, while α3 and β1 integrin mRNA expressions and podocyte density significantly decreased with increased proteinuria. Irbesartan obviously improved such changes.</p><p><b>CONCLUSION</b>In diabetic rats renal TGF-β1 can regulate α3 and β1 integrin mRNA expressions to reduce the number of podocytes, and inhibition of this pathway may be one of the mechanisms of the renal protective effect of irbesartan.</p>

Dose-effect relationship of irbsartan with the changes in the renal tissue structure in diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between the dosage of irbesartan and the renal tissue structure in diabetic rats.</p><p><b>METHODS</b>Male Wistar rats was given a single intraperitoneal dose (mg/kg) of streptozotocin to induce diabetes. The diabetic rats were randomized into 4 groups and received 4 weeks later 25 mg/kg (n=9), 50 mg/kg (n=9), 200 mg/kg (n=9) irbesartan intragastrically, or equal volume of water (model group, n=11) on a daily basis. Seven normal rats receiving with equal volume of water served as the normal control. All the rats were sacrificed after 8 weeks and the 24-hour albumin excretion, renal mass index and the volume of the glomerulus were measured.</p><p><b>RESULTS</b>The 24-hour albumin excretion, renal mass index and volume of the glomerulus in the 3 irbesartan groups were significantly decreased as compare with those in the model group; the reductions in 50 and 200 mg/kg irbesartan groups were significant greater than those in 25 mg/kg irbesartan group.</p><p><b>CONCLUSION</b>Irbesartan can decrease the 24-hour urinary albumin excretion and relive glomerulopathy in diabetic rats. Within a certain dose range, irbesartan produces a dose-dependent protective effect on the renal structures in the diabetic rats.</p>

Effect of irbesartan on ACE2 expression in diabetic rat myocardium / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of irbesartan on angiotensin-converting enzyme 2 (ACE2) mRNA expression in diabetic rat myocardium.</p><p><b>METHODS</b>Thirty 8-week-old male Wistar rats were randomly divided into control group (n=7), diabetic model group (n=14) and irbesartan group (n=9). Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), a blood glucose>16.7 mmol/L 72 h after the injection indicated successful establishment of diabetes. Four weeks after the modeling, the rats in irbesartan group were given 50 mg/kg irbesartan. ELISA was used to measure myocardial AngII content in the rats, and myocardial ACE2 mRNA expression was determined by real-time PCR.</p><p><b>RESULTS</b>Myocardial AngII level in the diabetic model group was significantly higher than that in the control group (P<0.001). Irbesartan administration significantly lowered cardiac AngII levels in the diabetic rats (P<0.001). The rats in irbesartan group showed significantly increased myocardial ACE2 mRNA expression compared with those in the control and diabetic rat groups (P<0.05).</p><p><b>CONCLUSION</b>Irbesartan can increase ACE2 mRNA expression in the myocardium, which might be one of the mechanisms underlying its effect in improving the cardiac function in diabetic rats.</p>