Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation

Objective Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A(2a) receptor (A(2a)R) in rats with myocardial ischemia-reperfusion (MI/R). Methods Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A(2)R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A(2a)R antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A(2a)R, collagen I, collagen III, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. Results Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen I, collagen III, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A(2a)R and collagen I and collagen III was found (p = 0.00). Conclusion SFI activated the A(2a)R to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.