Rosiglitazone protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression.

In this study, the effects of rosiglitazone on renal matrix metalloproteinase-9 (MMP-9) expression and its possible renoprotective mechanisms were investigated in streptozotocin-induced diabetic rats. We examined the urinary excretion rates of albumin (ALB), retinal-binding protein (RBP) and MMP-9 in control healthy rats (group C, n = 8), untreated diabetic rats (group D, n = 8) and diabetic rats treated with rosiglitazone (5mg/kg/day) (group R, n = 8) at eighth week. The renal tissue of diabetic rats was obtained for observing renal pathological changes by electron microscope and examining the expression of renal MMP-9 mRNA by RT-PCR. Our results showed that urinary excretion rates of MMP-9. ALB and RBP were significantly increased concurrently with the expression of renal MMP-9mRNA in group D compared with those of group C. Rosiglitazone significantly reduced urinary excretion rates of ALB, RBP and MMP-9 as well as the expression of renal MMP-9 mRNA. In addition, urinary excretion rate of MMP-9 showed positive relationship with urinary excretion rates of ALB and RBP. In conclusion, rosiglitazone definitely protects diabetic rats against renal injury, which may be partly associated with decreasing expression of renal MMP-9 mRNA and urinary MMP-9 production.

[Effect of spironolactone on left ventricular remodeling in patients with acute myocardial infarction].

OBJECTIVE: To investigate the effect of spironolactone on left ventricular remodeling (LVRM) in patients with acute myocardial infarction. METHODS: In this multicentric, randomized, controlled study, spironolactone 40 mg/d was randomly administered in addition to the routine treatment for patients with AMI. During the 6 months the serum PIIINP, BNP and echocardiography were examined in all patients to assess myocardial fibrosis, LV function and volume. RESULTS: A total of 88 AMI patients entered the study came from 4 hospitals in Shijiazhuang. There were 43 patients with anterior MI and 45 with inferior MI. In anterior MI group 23 patients received spironolactone and 20 accepted the routine treatment. In inferior MI group 23 received spironolactone and 22 accepted the routine treatment. In anterior MI group: (1) At 3rd, 6th month PIIINP and BNP serum levels were significantly lower in the spironolactone group compared with those in control group [PIIINP (260.2 +/- 59.9) vs (328.0 +/- 70.3) ng/L, P = 0.001, (197.1 +/- 46.3) vs (266.7 +/- 52.4) ng/L, P < 0.001], [BNP (347.4 +/- 84.0) vs (430.1 +/- 62.9) ng/L, P < 0.001, (243.7 +/- 79.7) vs (334.6 +/- 62.8) ng/L, P < 0.001]; (2) There were smaller LVEDD and LVESD in spironolactone group compared with those in control group after 6 months intervention [(51.0 +/- 5.5) vs (55.6 +/- 4.5) mm, P = 0.005, (35.7 +/- 4.6) vs (39.1 +/- 5.6) mm, P = 0.046]. However, in inferior MI group: (1) There were no significant differences in PIIINP and BNP values between the two groups after 6 months intervention; (2) There were no significant differences in the LVEDD, LVESD, LVEF after 6 months treatment. CONCLUSION: (1) In patients with anterior MI, spironolactone combined with the routine treatment could inhibit myocardial fibrosis and left ventricular dilation and prevent LVRM. (2) In patients with inferior MI, no significant difference in prevention of LVRM was found between the spironolactone combined with the routine treatment and the routine treatment alone.