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 granu- locyte 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 interven- tion, 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.