Abstract:

Objective To investigate the influence of insulin resistance on the ventricular remodeling, and to observe the intervention effect of rosuvastatin and explore its possible mechanism. Methods Forty male LDLR^－/－ mice aged 6 weeks were randomized into control group (NC group, fed with normal diet), high fat and high fructose diet group (HFF group, fed with normal diet+21.1% fat+20% fructose), rosuvastatin intervention group(HFFR group, intervention with rosuvastatin on the basis of that in HFF group) and rosuvastatin and mevalonic acid intervention group (HFFRMA group, fed with mevalonic acid on the basis of that in HFFR group), with 10 mice in each group. Mice were sacrificed 12 weeks after treatment, the fasting blood sugar (FBS) was determined by oxygen electrode method, fasting plasma insulin (FINS) was detected by ELISA, homeostasis model insulin resistance index (HOMA-IR) and left ventricular weight index (LVWI) were calculated, collagen volume fraction (CVF) of myocardial tissues was calculated with Picric-Sirius Red staining, and the expression of PPARα and MMP-9 protein in myocardial tissues was detected by Western blotting. Results FBS, FINS, HOMA-IR, LVWI, CVF and the expression of PPARα and MMP-9 protein in HFF group, HFFR group and HFFRMA group were significantly higher than those in NC group(P<0.05). After treatment with rosuvastatin, FBS, FINS and HOMA-IR in HFFR group and HFFRMA group were significantly improved, and LVWI, CVF and the expression of PPARα and MMP-9 protein in HFFR group and HFFRMA group were significantly lower than those in HFF group (P<0.05). However, there was no significant difference in these parameters between HFFR group and HFFRMA group (P>0.05). Conclusion Insulin resistance can be induced in LDLR^－/－ mice 12 weeks after high fat and high fructose diet. Insulin resistance may contribute to myocardial fibrosis and ventricular remodeling. Rosuvastatin can inhibit ventricular remodeling and improve insulin resistance, and the mechanism may be associated with the down-regulation of expression of MMP-9 and PPARα protein, which is independent of lipid-lowering effect.

Key words: insulin resistance, ventricular remodeling, rosuvastatin