摘要：Rosiglitazone, an important peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, improves left ventricular (LV) hypertrophy in diet-induced hypercholesterolemic rats. However, the effects and underlying mechanisms of rosiglitazone on myocardial remodeling in spontaneous hypertension rats (SHRs) are unclear. Twenty male 8-week-old SHRs were randomly divided into two groups: one treated with oral saline (n=10) and the other treated with rosiglitazone (5 mg kg(-1) day(-1), n=10). Ten age-matched Wistar-Kyoto rats were selected as a normal control group. Echocardiography, immunohistochemistry, real-time reverse transcriptase-PCR and western blot analysis were performed to assess the effects of rosiglitazone. After 16 weeks of treatment, LV hypertrophy was significantly attenuated by rosiglitazone (LV weight/body weight, 2.35 +/- 0.11 vs. 2.56 +/- 0.14 mg g(-1)). According to the echocardiography results, thickening of the LV wall was reduced, and mid-wall fractional shortening was improved by rosiglitazone. Similarly, the excessive collagen deposition and upregulation of collagen I and collagen III seen in SHRs receiving saline were significantly attenuated in SHRs receiving rosiglitazone. In addition, rosiglitazone treatment increased the activity of matrix metalloproteinase-9 (MMP-9) and normalized the MMP-9/tissue inhibitor of metalloproteinase-1 ratio. Furthermore, activator protein-1 (AP-1) activation and nuclear factor-kappa B (NF-kappa B) expression were suppressed in the rosiglitazone-treated group. These results demonstrate that the PPAR-gamma agonist rosiglitazone had beneficial effects on myocardial remodeling in SHRs by way of decreasing AP-1 activation and NF-kappa B expression, which may help in further inhibiting transcription of the downstream genes involved in the pathogenesis of myocardial remodeling induced by hypertension. Hypertension Research (2011) 34, 354-360; doi:10.1038/hr.2010.242; published online 20 January 2011
