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Effects of combined MCA and G-CSF treatment on myocardial fibrosis and apoptosis gene expression in rats with diastolic heart failure

Objective: To explore the therapeutic effect of combining meglumine cyclic adenosine (MCA) with granulocyte colony-stimulating factor (G-CSF) in treating rats with diastolic heart failure (DHF). Methods: A total of 40 Sprague Dawley (SD) male rats were evenly divided into 4 groups: the Sham operation group (Control), the Model group (DHF), the MCA group (MCA) and the MCA combined with G-CSF group (MCA+G-CSF). The MCAgroup was given 30 mg/kg/d (body weight) MCA by intragastric injection for 15 days. The MCA+G-CSF group was treated with 30 mg/kg/d MCA and 100 μg/kg/d G-CSF by intragastric and subcutaneous injection, respectively, for 15 days. The Control group and Model group were given equal volumes of saline solution. After 15 days of drug intervention, cardiac function was measured by echocardiography using a BL-420-F physiological recorder; BcL-2 and Bax expression was measured by RT-PCR and western blotting; and serum BNP levels were determined using an ELISA. Results: Compared with fibrosis in the MCA group, myocardial fibrosis was significantly decreased in the MCA+G-CSF group. Treatment with G-CSF plus MCA significantly promoted BcL-2 expression (mRNA, 334.26 ± 28.12 vs. 279.82 ± 18.56; protein, 1.83 ± 0.26 vs. 1.18 ± 0.16) (P<0.05) and reduced Bax expression (mRNA, 103.42 ± 7.62 vs. 182.46 ± 15.83; protein, 0.81 ± 0.06 vs. 1.37 ± 0.14) (P<0.05) and serum BNP levels (328.85 ± 18.39 vs. 396.58 ± 26.48) (P<0.05). Conclusion: G-CSF may regulate cell apoptosis in DHF rats and reduce their serum BNP levels; coupling MCA with G-CSF can significantly improve cardiac diastolic function in DHF rats and is associated with a better therapeutic effect than treatment with MCA alone.