Effect and Mechanism of Leonurine on Rats with Ventricular Remodeling Induced by Isoproterenol

OBJECTIVE To observe the effect of leonurine on rats with ventricular remodeling induced by isoproterenol(ISO) and to explore the possible mechanism involved. METHODS SD rats (n=10) were used as normal control group， and 80 rats were given ISO by intraperitoneal injection daily for 2 weeks to establish the model of ventricular remodeling. The model rats were divided into 5 groups randomly as model group， low-dose leonurine (7.5 mg/(kg·d)) group， middle-dose leonurine (15 mg/(kg·d)) group， high-dose leonurine (30 mg/(kg·d)) group and p38MAPK inhibitor (0.3 mg/(kg·d)) group. After the treatment for 2 weeks， the pathological change of left ventricular myocardial tissues was observed by HE staining，and the expression of TGF-β1 was determined by the method of immunohistochemistry. The serum concentrations of ET-1 and NO were measured by ELISA and nitrate reductase methods， respectively. The expression of p38MAPK， MEF2，β-MHC and α-MHC mRNA was detected by qPCR， and the protein expression of ET-1， p-p38MAPK and MEF2 was determined by Western blot. RESULTS Compared with model group， the pathological change of ventricular remodeling in high-dose leonurine group was attenuated， and the serum concentrations of NO and the mRNA expression of α-MHC in left ventricular myocardial tissues of high-dose leonurine group were higher (P<0.05).The expression of TGF-β1， the serum concentrations of ET-1， the mRNA expression of p38MAPK，MEF2 and β-MHC mRNA， and the protein expression of ET-1， p-p38MAPK and MEF2 were lower than those in model group (P<0.05). CONCLUSION Leonurine attenuates ventricular remodeling in the rats induced by ISO， and it is potentially associated with inhibiting p38MAPK/MEF2 signaling pathway.