The changes of hemodynamics and the effect of RHO kinase regulated by butylphthalein on apoptosis in acute myocardial infarction

Abstract: Background: Cardiomyocyte apoptosis plays a critical role in ventricular remodeling and heart failure following acute myocardial infarction (AMI). The Rho kinase signaling pathway is known to be involved in this pathological process. Butylphthalein, a compound with neuroprotective effects, may exert cardioprotective effects by regulating this pathway. Objective: This study aims to investigate the effects of butylphthalein on hemodynamic parameters and cardiomyocyte apoptosis in a rat model of AMI and to explore whether these effects are mediated through the Rho kinase signaling pathway. Methods: Fifty SD rats were randomly divided into five groups: Sham, AMI model, butylphthalein, fasudil (a Rho kinase inhibitor) and combination therapy. AMI was induced by ligation of the left anterior descending coronary artery. Two weeks post-surgery, hemodynamic parameters—including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximal rate of rise and fall of ventricular pressure (±dp/dtmax)—were measured. Cardiomyocyte apoptosis was assessed using TUNEL staining. The expression levels of Bcl-2, Bax, RhoA, ROCK1 and the p-MYPT1/MYPT1 ratio were detected by Western blot. Results: Rats in the AMI model group exhibited significant hemodynamic impairment and increased cardiomyocyte apoptosis. Compared with the model group, butylphthalein treatment significantly improved LVSP and ±dp/dtmax, reduced LVEDP, decreased the number of TUNEL-positive cells, upregulated Bcl-2 expression, downregulated Bax expression and suppressed the expression of RhoA/ROCK1 and the p-MYPT1/MYPT1 ratio (all P<0.05). The combination of butylphthalein and fasudil resulted in enhanced therapeutic effects, suggesting a synergistic inhibition of Rho kinase activity. Conclusion: Butylphthalein attenuates cardiomyocyte apoptosis and improves cardiac function in rats with AMI, likely through inhibition of the Rho kinase signaling pathway. These findings support its potential as a therapeutic agent for AMI.All experiments were performed on male Sprague-Dawley rats (n=50).