Farrerol exhibits the protective effect on myocardial injury via regulating CYP2J2/EETs axis in rats with doxorubicin-induced dilated cardiomyopathy
Objective To investigate the effect of Farrerol on the myocardial injury induced by doxorubicin(Dox)in rats with dilated cardiomyopathy(DCM).Methods SD rats were given intraperitoneal injection of 2.5 mg·kg-1 Dox to establish the DCM model.The rats were randomly divided into normal group(given the same amount of 0.9％NaCl by gavage),model group(establish the DCM model),experimental-L group(given 12.5 mg·kg-1·d-1 farrerol by gavage),experimental-H group(given 50 mg·kg-1·d-1 farrerol by by gavage),combine group(given 50 mg·kg-1·d-1 farrerol+1.5 mg·kg-1·d-1 C26 by gavage).Cardiac function was detected after drug intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of 11,12-EET and 14,15-EET,the products of epoxyeicosatrienoic acids(EETs)in myocardial tissue.Western blot was used to detect the protein expression of cytochrome P450 cyclooxygenase 2J2(CYP2J2)in myocardial tissue.Results The left ventricular end diastolic diameter(LVEDD)of normal group,model group,experimental-L,-H groups and combine group were(5.44±0.15),(6.23±0.36),(6.14±0.58),(5.66±0.22)and(6.16±0.35)mm;the left ventricular ejection fraction(LVEF)were(83.36±2.05)％,(59.66±5.93)％,(56.63±3.20)％,(74.67±3.33)％and(61.95±5.38)％;the creatine kinase(CK)levels were(346.10±49.51),(874.50±85.52),(860.30±46.38),(371.20±50.83)and(789.44±86.48)U·L-1;the apoptosis rates of cardiomyocytes were(2.34±0.91)％,(20.11±3.85)％,(18.94±1.65)％,(10.64±1.23)％and(17.56±2.02)％;the11,12-EET levels were(28.79±4.21),(9.69±3.43),(10.71±3.89),(21.85±5.46)and(12.94±4.60)pg·mg-1;the 14,15-EET levels were(33.12±3.47),(12.75±4.34),(13.27±7.20),(25.18±6.21)and(16.25±2.08)pg·mg-1;the CYP2J2 protein expression levels were 1.20±0.08,0.19±0.04,0.19±0.05,0.85±0.05 and 0.33±0.05,respectively.The differences of above indicators were statistically significant between the model group and the normal group,between the experimental-H group and the model group,as well as between the combine group and the experimental-H group(all P＜0.01).Conclusion Farrerol can improve Dox-induced myocardial injury in DCM rats,and its mechanism may be related to the activation of the CYP2J2/EETs pathway.
万方数据
维普
