Abstract: Objective: To explore the protective effect and underlying mechanism of Rosa roxburghii Tratt polysaccharides on isoproterenol (ISO)-induced myocardial ischemia (MI) in mice. Methods: Forty male C57BL/6 mice were equally and randomly divided into five groups: control, model, propranolol (30 mg/kg), low- and high-dose R. roxburghii Tratt polysaccharides (50 and 100 mg/kg). Mice were pretreated with R. roxburghii Tratt polysaccharides for seven days followed by intraperitoneal injection of isoprenaline (ISO, 10 mL/kg) or physiological saline for seven days. Electrocardiograms were recorded 1 h after the last injection. The mice were anesthetized and hearts were excised to calculate cardiac index. Hematoxylin-eosin (HE) staining was used to evaluate myocardial pathological changes. The area of myocardial infarction was detected by 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Serum lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were detected by biochemical kits. The protein expression of NADPH oxidase 2 (NOX2), B-cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), caspase 3, nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH-related protein 1 (Keap1) and heme oxygenase 1 (HO-1) in myocardial tissues were detected by Western blot. Results: Compared with the control group, heart coefficient was significantly increased in the model group and the ST segment of electrocardiogram was significantly elevated. Significantly pathological changes and increased myocardial infarction were found in the myocardial tissue of mice in the model group. Serum MDA and LDH levels were increased (P < 0.001) and SOD activity was inhibited in the model group (P < 0.05). The protein expressions of Nrf2, HO-1 and Bcl2 were significantly down-regulated (P < 0.05 or P < 0.01), while those of Keap1, NOX2, Bax and caspase 3 were significantly up-regulated in the model mice (P < 0.05 or P < 0.01). The ST segment of electrocardiogram was lowered, and myocardial pathological changes were restored in the polysaccharide treatment group compared with the model group. In addition, serum MDA and LDH levels were significantly decreased (P < 0.001) and SOD activity was significantly increased (P < 0.01 or P < 0.001). The protein expressions of Nrf2, HO-1 and Bcl2 were significantly up-regulated (P < 0.05 or P < 0.01), while those of Keap1, NOX2, Bax and caspase 3 were significantly down-regulated (P < 0.05, P < 0.01 or P < 0.001). Conclusion: R. roxburghii Tratt polysaccharides ameliorate ISO-induced myocardial ischemia though reducing oxidative stress, regulating caspase-3, Bax and Bcl2 protein expressions and suppressing myocardial cell apoptosis via the Keap1-Nrf2 signaling pathway.

Key words: Rosa roxburghii Tratt polysaccharides; myocardial ischemia; isoprenaline; oxidative stress; apoptosis