Abstract: Abstract: Objective To observe the effects of long-term aerobic training on cardiac fibrosis in spontaneously hypertensive rats (SHR) and to investigate the role and mechanism of collagen metabolism regulators such as transforming growth factor - β1 (TGF - β1), connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2). Methods Thirty male SHRs were randomly separated to rest control (SHRRC) or aerobic training (SHR-AT) groups, and 15 Wistar-Kyoto rats were used as normotensive control (NC) group. Animals in NC and SHR-RC groups were kept silent at cage while those in SHR-AT group undertook treadmill exercise for 24 weeks. At the end of experiment, a series of measurements were determined for caudal artery pressure by non-invasive blood pressure tester, cardiac structure and function were detected by echocardiogram, cardiac collagen volumetric fraction (CVF) was determined by Masson dyeing, mRNA expression levels of atrial natriuretic factor (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected by real-time Q-PCR, and protein expressions of TGF-β1, CTGF, MMP- 2 (including 64 ku and 72 ku isoforms), TIMP-2 and alpha-smooth muscle actin (α-SMA) were detected by Western blot assay. Results Compared with NC group, the dilated cardiac chamber with thinner ventricular wall was found in rats of SHR-RC group, and the cardiac CVF increased (P＜0.05), cardiac function decreased (P＜0.05), and ANP, BNP and β- MHC mRNA as well as TGF-β1, CTGF, TIMP-2 and α-SMA proteins upregulated (P＜0.05). Also 64 ku MMP-2 and 64 ku MMP-2 / TIMP-2 ratio reduced (P＜0.05). Compared with SHR-RC group, animals in SHR-AT group showed alleviated cardiac chamber dilation, reduced cardiac CVF (P＜0.05), enhanced cardiac function (P＜0.05), downregulated ANP, BNP and β-MHC mRNA and α-SMA protein (P＜0.05), increased 64 ku MMP-2 and 64 ku MMP-2/TIMP-2 ratio (P＜0.05). There were no significant changes in TGF-β1, CTGF and TIMP-2 protein expressions (P＞0.05). Conclusion Long-term regular aerobic training can improve cardiac fibrosis and delay cardiac remodeling and heart failure progression in SHR, and the mechanism is related with the augment of collagen degradation (however, no effect on collagen synthesis) and inhibition of differentiation from fibroblasts into myofibroblasts

Key words: aerobic training, hypertension, rats, collagen, myocardial fibrosis