Abstract: AIM: To investigate whether the ligand of peroxisome Proliferator-activated receptor γ(PPARγ), rosiglitazone (ROS), can reverse myocardial interstitial fibrosis in rats with heart failure. METHODS: Sixty weight-matched adult male Wistar rats were randomly divided into 3 groups as follows:(1)the CHF group, in which 2.5 mg/kg of adriamycin (ADR)was weekly injected via a tail vein for 10 weeks (n=25);(2)the ROS group, concomitant ROS and ADR, in which ROS as a PPARγligand was administered by daily gavage at a dose of 3 mg·kg^-1·d^-1(n=25);(3)the control group (n=10).The cardiac function was evaluated by echocardiographic method.The plasma concentrations of TNF-α, Angiotensin II (Ang II)and Aldsterone (Ald)were determined by immunoradiometric assay at 12 weeks after treatment.The hydroxyproline and collagen content were determined by the methods of Chloramines T and Picric acid-Sirius red staining techniques.The pathological change was analyzed by histological hematoxylin-eosin staining. RESULTS: The mortality of ROS-treated rats was significantly lower than that of CHF group (20% versus 40%, P<0.01).The plasma concentrations of TNF-α, Ang II and Ald were higher in the CHF group than those in the control group (P<0.01), which was decreased by ROS treatment.The hydroxyproline and collagen content were increased in CHF group(both P<0.01), but decreased in ROS group.The myocardial collagen of left ventricle increased and the collagen volume fraction (CVF)increased significantly, which were partly reversed by ROS treatment(P<0.01).The pathological results showed there was changes of cardiomyopathy in CHF group, ROS reversed the pathological changes of left ventricular myocardium of CHF. CONCLUSION: Pretreatment with PPARγligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α, Ang II and Ald.

Key words: peroxisome proliferator activated receptor γ, rosiglitazone, adriamycin, heart failure, interstitial fibrosis