Effect of Yiqihuoxue prescription on myocardial energy metabolism after myocardial infarction via cross talk of liver kinase B1-depen- dent Notch1 and adenosine 5 ' -monophosphate-activated protein ki- nase

OBJECTIVE: To investigate the effect of Yiqihuoxue prescription (YQHX) from Traditional Chinese Medi- cine (TCM) on myocardial glucose and lipid metab- olism after myocardial infarction via the cross talk between the liver kinase B1 (LKB1)-dependent Notch1 and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). YQHX was prepared with substances with properties that ben- efit, to activate blood circulation based on the TCM theory. METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The ani- mals were randomly divided into a myocardial in- farction (MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibi- tor (DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the rele- vant indexes were examined on weeks 1 and 4. Changes in cardiac structure and function were ex- amined by echocardiography. The glucose and free fatty acids (FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK mRNA was ex- amined by a real-time fluorescence quantitative method. The expression of glucose transporter 4 (GLUT4), and the expression of total acetyl-CoA car- boxylase (ACC) and its phosphorylation were exam- ined bywestern blotting. RESULTS: Compared with the sham group, the ex- pression of Notch, LKB1 and AMPK mRNA in the MI group was lower. Compared with the MI group, the expression of these mRNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and pACC decreased in the MI group. On week 1, the expression of pACC protein was higher. In the DAPT group, the expres- sion of pACC protein decreased. Compared with the YQHX group, the expression of pACC protein in the DAPT + YQHX group was lower. On week 4, compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindo-pril group was higher. The expression of GLUT4 pro- tein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC pro- tein between the groups. CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocar- dial tissue after myocardial infarction. Furthermore, it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via dif- ferent mechanisms and protecting the heart.