Key result
The combination of Chuanxiong and Chishao markedly improved LVEF and decreased the percentage of MI area compared with the model group after 21 days of treatment.
Why the study?
The cardioprotective mechanism by which the combination of Chuanxiong and Chishao promotes angiogenesis in ischemic myocardium was not fully understood.
Does the combination of Chuanxiong and Chishao improve cardiac function and promote angiogenesis in a mouse model of myocardial infarction?
Does the combination of Chuanxiong and Chishao improve cardiac function and promote angiogenesis in a mouse model of myocardial infarction?
The combination of Chuanxiong and Chishao improves cardiac function and promotes angiogenesis in ischemic myocardium, potentially through Notch signalling and stem cell mobilization.
Objective. To study the cardioprotective mechanism by which the combination of Chuanxiong (CX) and Chishao (CS) promotes angiogenesis.Methods. Myocardial infarction (MI) mouse models were induced by ligation of the left anterior descending coronary artery. The effects on cardiac function were evaluated in the perindopril tert-butylamine group (PB group) (3 mg/kg/d), CX group (55 mg/kg/d), CS group (55 mg/kg/d), and CX and CS combination (CX-CS) group (27.5 mg/kg/d CX plus 27.5 mg/kg/d CS). RO4929097, an inhibitor of Notchγsecretase, was used (10 mg/kg/d) to explore the role of Notch signalling in the CX-CS-induced promotion of angiogenesis in the myocardial infarcted border zone (IBZ). The left ventricular ejection fraction (LVEF) and percentage of MI area were evaluated with animal ultrasound and Masson staining. The average optical densities (AODs) of CD31 and vWF in the myocardial IBZ were detected by immunofluorescence. Angiogenesis-related proteins including hypoxia-inducible factor 1-alpha (HIF-1α), fibroblast growth factor receptor 1 (FGFR-1), Notch1 and Notch intracellular domain (NICD), and stem cell mobilization-related proteins including stromal cell-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR-4), and cardiotrophin1 were detected by western blot analysis.Results. Compared with the model group, the CX-CS and PB groups both showed markedly improved LVEF and decreased percentage of MI area after 21 days of treatment. Although the CX group and CS group showed increased LVEF and decreased MI areas compared with the model group, the difference was not significant. The AOD of CD31 in the IBZ in both the model and the CX-CS-I group was markedly reduced compared with that in the sham group. CX-CS significantly increased the CD31 AOD in the IBZ and decreased the AODs of CD31 and vWF in the infarct zone compared with those in the model group. The expression of HIF-1αin both the model group and the CX-CS group was higher than that in the sham group. Compared with the model group, the expression of FGFR-1, SDF-1, cardiotrophin1, Notch1, and NICD was increased in the CX-CS group. Notch1 and NICD expression in the CX-CS-I group was reduced compared with that in the CX-CS group.Conclusions. The combination of CX and CS protected cardiomyocytes in the IBZ better than CX or CS alone. The mechanism by which CX-CS protects ischemic myocardium may be related to the proangiogenesis effect of CX-CS exerted through Notch signalling and the mobilization of stem cells to the IBZ.
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Shi et al. (2019) studied Myocardial infarction (mouse models). Combination of Chuanxiong (CX) and Chishao (CS) vs. Model group was evaluated on Left ventricular ejection fraction (LVEF) and percentage of MI area. The combination of Chuanxiong and Chishao markedly improved LVEF and decreased the percentage of MI area compared with the model group after 21 days of treatment.
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