Objectives To explore the changes of aortic morphosis and expression of transforming growth factor-β1 (TGF-β1), smad3, collagen-I (COL-I) and collagen-III (COL-III) in the fructose-induced metabolic syndromic rats, and the effect of PPAR-α / γ agonists on their.
Methods Metabolic syndrome was induced in 44 male Sprague-Dawley rats by feeding high fructose (60% fructose) diet for 10 weeks. Then model rats of metabolic syndrome were randomly divided into model control group (MC group, n = 11), fenofibrate group (FEN group, n = 11), were treated with fenofibrate 30 mg.kg-1.day-1, pioglitazone group (PIO group, n = 11), were treated with pioglitazone 3 mg.kg-1.day-1, and fenofibrate adding pioglitazone group (FEN + PIO group, n = 11), were treated with fenofibrate 30 mg.kg-1.day-1 and pioglitazone 3 mg.kg-1.day-1, and another 10 male Sprague-Dawley rats constituted control group (NC group, n = 10) and constantly consumed standard rat chow. After 4 weeks treatment, rats were killed, and their aortic morphology were detected by hemotoxylin and eosin staining, expression levels of protein of TGF- β1, Smad3, COL-, COL-III was detected by Western Blot.
Results High fructose diet successfully induced a rat model with metabolic syndrome, characterised by a significant increase in systolic blood pressure, serumtriglycerides, free fatty acids and insulin compared with the control group. In addition, compared with control group, the expression levels of TGF-β1, Smad3, COL-I and COL-III protein all increased (P<0.01), and the aorticintima-media thickness was increased, and structural disorder was observed in aortas of MSrats. Treatment with fenofibrate, pioglitazone, and fenofibrate adding pioglitazone all down-regulated the expression levels of TGF-β1, Smad3, COL-I protein increased of rats with metabolic syndrome compared with rats in MC group (P < 0.01 or P < 0.05). But compared to fenofibrate group, rats in PIO group and FEN + PIO group exhibited a lower expression levels of TGF-β1, Smad3, COL-I and COL-III protein in their aortas (P < 0.01 or P < 0.05), while when compared to PIO group the protein expression level of COL-I in rat’s aortas of FEN + PIO group was decreased (P < 0.05). Treatment with fenofibrate or pioglitazone all amended rat’s aortic intima-media thickness in FEN group and PIO group, and improved their aortic structure compare with raisin MC group, which changes were more obviously in FEN + PIO groups.
Conclusions Treatment with fenofibrate or pioglitazone singly can inhibit aorticpathologic remodelling in MS rats by inhibiting the synthesis of collagen which induced by the signal transduction pathway of TGF-β1/Smads, and the effects was more significant when treated by combining with fenofibrate and pioglitazone.