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Effect of Epimedii Folium Total Flavonoids on Angiogenesis of Ischemic Myocardium in Rats After Acute Myocardial Infarction / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 40-47, 2021.
Article in Chinese | WPRIM | ID: wpr-906391
ABSTRACT

Objective:

To observe the effect of total flavonoids from Epimedii Folium (TEF) on the angiogenesis of ischemic myocardium in rats after acute myocardial infarction (AMI) and discuss its molecular biological mechanism of attenuating myocardial ischemia and improving cardiac function.

Method:

AMI in rats was induced through the ligation of left anterior descending coronary artery. All male SD rats were randomized into sham-operated group, model group, diltiazem group (10 mg·kg<sup>-1</sup>·d<sup>-1</sup>), and TEF low-dose and high-dose groups (100 and 200 mg·kg<sup>-1</sup>·d<sup>-1</sup>), with 8 rats in each group. After modeling, rats in the diltiazem group and TEF groups were given corresponding doses of diltiazem and TEF, respectively, and those in the model group and sham-operated group received normal saline of equivalent volume, once a day for 7 days. After the administration, VisualSonics Vevo2100 imaging system was used to detect the cardiac structure and function and hematoxylin-eosin (HE) staining to observe the histomorphological changes in myocardial ischemic area. Immunohistochemistry was employed to analyze the expression of CD31 and <italic>α</italic>-smooth muscle actin (<italic>α</italic>-SMA) in ischemic myocardium and Western blot to detect the expression of vascular endothelial growth factor-receptor 2 (VEGF-R2) and phosphorylation of protein kinase B (Akt) in ischemic myocardium. Real-time PCR was applied to quantify the mRNA levels of vascular endothelial growth factorVEGF) and basic fibroblast growth factor (bFGF).

Result:

Compared with the sham-operated group, the model group demonstrated significant increase in left ventricular systolic diameter (LVIDs), left ventricular internal diameter at end-diastole (LVIDd), left ventricular end-systolic volume (LVEVs), and left ventricular end-diastolic volume (LVEVd), significant decrease in End-systolic thickness of left ventricular anterior wall (LVAWs), end-diastolic thickness of left ventricle anterior wall (LVAWd), end systolic thickness of left ventricular posterior wall (LVPWs), stroke volume (SV), ejection fraction (EF), fractional shortening (FS), and cardiac output (CO), obvious pathological changes in the ischemic myocardium, and plummet of the expression of CD31 and <italic>α</italic>-SMA (<italic>P</italic><0.01), Akt phosphorylation level, protein level of VEGF-R2, and mRNA levels of VEGF and bFGF (<italic>P</italic><0.05, <italic>P</italic><0.01). High-dose TEF significantly alleviated the pathological changes of ischemic myocardium as compared with the model group. Moreover, TEF high-dose group showed significantly lower levels of LVIDs, LVIDd, LVEVs, and LVEVd, significantly higher levels of LVAWs, LVAWd, LVPWs, SV, EF, FS, and CO, higher expression of CD31 and <italic>α</italic>-SMA (<italic>P</italic><0.05, <italic>P</italic><0.01), and higher levels of VEGF-R2 protein, phosphorylated Akt, and VEGF and bFGF mRNA than the model group (<italic>P</italic><0.05, <italic>P</italic><0.01).

Conclusion:

TEF can effectively improve myocardial perfusion in peri-myocardial infarction area and attenuate ventricular remodeling and heart failure after AMI by up-regulating the expression of bFGF, VEGF, and VEGF-R2 in ischemic myocardium following AMI and activating phosphatidylinositol 3-kinases (PI3K)/Akt/VEGF signaling transduction pathway which can promote angiogenesis in ischemic myocardium.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Controlled clinical trial / Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Controlled clinical trial / Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article