Abstract: Objective To investigate the effects of all-trans retinoic acid (ATRA) on myocardial fibrosis and myocardial remodeling induced by isoproterenol (ISO) in rats, and to analyze itsmechanism. Methods The rats were randomly divided into 4 groups: control group, ISO group,ATRA + ISO group, 4-phenylbutyric acid (4-PBA) + ISO group, with 10 rats in each group. Rats in the ATRA + ISO group and the 4-PBA + ISO group were administrated with ATRA and 4-PBA through intraperitoneal injection respectively. Rats in the ISO group, the ATRA + ISO group and the 4-PBA + ISO group were administrated with ISO through subcutaneous injection on the back. The left ventricular internal diameter in diastole ( LVIDd), left ventricular internal diameter in systole ( LVIDs), left ventricular ejection fraction (EF) and fractional shortening (FS) were detected by cardiac ultrasound. The body weight, whole heart mass and left ventricular mass of rats were weighed, and the whole heart mass index ( HMI) and left ventricular mass index ( LVMI) were calculated. The level of serum N-terminal pro B type natriuretic peptide ( NT-proBNP) was determined by ELISA. HE staining and Masson staining were used to observe the histopathological changes and the degree of collagen fibrosis in rat myocardial tissues, respectively. The protein expression levels of G protein-coupled receptor 78 (GRP78), C / EBP homologous protein (CHOP), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), and transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), Collagen-I and Collagen-Ⅲ in myocardial tissues were determined by Western blotting. Results When compared with those in the control group, the EF and FS in the ISO group were significantly decreased (P < 0. 05), the LVIDd, LVIDs, HMI and LVMI were significantly increased (P< 0. 05), the level of serum NT-proBNP was significantly increased (P< 0. 05), thepathological injury of myocardial tissues was observed, the areas with collagen fiber had significantlyincreased (P< 0. 05), the protein expression levels of GRP78, CHOP, PERK, P-EIF2α, TGF-β1, α-SMA, Collagen Ⅰ and Collagen Ⅲ in the myocardial tissues were significantly up-regulated(P< 0. 05). When compared with those in the ISO group, the EF and FS in the ATRA + ISO group and the 4-PBA + ISO group were significantly increased ( P < 0. 05), the LVIDd, LVIDs, HMI and LVMI were significantly decreased (P< 0. 05), and the level of serum NT-proBNP was significantly decreased (P< 0. 05), the degree of myocardial injury was significantly reduced, the area with collagen fiber had significantly reduced ( P < 0. 05 ), and the protein expression levels ofGRP78, CHOP, PERK, P-EIF2α, TGF-β1, α-SMA, Collagen Ⅰ and Collagen Ⅲ in the myocardial tissue were significantly down-regulated (P< 0. 05). Conclusion ATRA can alleviate ISOinduced myocardial injury and fibrosis, inhibit myocardial remodeling and improve cardiac function through the inhibition of endoplasmic reticulum stress response.

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