Huoxue Wentong Prescription Ameliorates Post-myocardial Infarction Ventricular Remodeling in Rats via HIF-1α/TGF-β1/POSTN-mediated Regulation of EndMT
10.13422/j.cnki.syfjx.20260433
- VernacularTitle:基于HIF-1α/TGF-β1/POSTN调控EndMT探讨活血温通方改善大鼠心肌梗死后心室重塑的机制
- Author:
Xiaoning SUN
1
;
Xiaoxiao ZHANG
2
;
Cheng LI
3
;
Qingqing WANG
3
;
Jianguo LIN
4
;
Mingyue WANG
5
;
Ying YANG
1
;
Kuiwu YAO
2
Author Information
1. Affiliated Hospital of Liaoning University of Traditional Chinese Medicine （TCM）， Shenyang 110000，China
2. Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Beijing 100053，China
3. Eye Hospital， China Academy of Chinese Medical Sciences， Beijing 100040，China
4. Zhejiang Provincial Hospital of TCM， Hangzhou 310060，China
5. School of Basic Medical Sciences， Peking University， Beijing 100191，China
- Publication Type:Journal Article
- Keywords:
Huoxue Wentong prescription;
myocardial infarction;
ventricular remodeling;
endothelial-to-mesenchymal transition （EndMT）;
hypoxia-inducible factor-1α （HIF-1α）/transforming growth factor-β1 （TGF-β1）/periostin （POSTN） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(22):148-158
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription （HXWT） ameliorates post-myocardial infarction （MI） ventricular remodeling by regulating endothelial-to-mesenchymal transition （EndMT） via the hypoxia-inducible factor-1α （HIF-1α）/transforming growth factor-β1 （TGF-β1）/periostin （POSTN） signaling pathway. MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group （n=10） and a modeling group （n=70）. The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group， a sacubitril/valsartan （Entresto， 0.021 g·kg-1） group， and low， medium， and high-dose （4.15， 8.30， and 16.60 g·kg-1， respectively） HXWTF groups （n=10 per group）. From postoperative day 2， rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks， and those in sham and model groups received an equal volume of normal saline. After intervention， general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end diastolic diameter （LVEDD）， and left ventricular end systolic diameter （LVESD）. Hematoxylin and eosin （HE） staining was employed to evaluate myocardial histopathology， and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide （BNP）， interleukin （IL）-6， IL-10， and matrix metalloproteinase-9 （MMP-9） were determined by enzyme-linked immunosorbent assay （ELISA）. Collagen type Ⅰ （ColⅠ） expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 （CD31） and α-smooth muscle actin （α-SMA）. Western blot was performed to quantify the expression of collagen type Ⅰ α2 （Col1A2）， VE-cadherin， CD31， α-SMA， HIF-1α， TGF-β1， and POSTN. ResultsCompared with the sham group， the model group exhibited thinning and collapse of the left ventricular wall， decreased LVEF and LVFS and increased LVEDD and LVESD （P<0.01）， disrupted myocardial fibers with marked inflammatory cell infiltration， increased collagen deposition， enhanced ColⅠ immunoreactivity， elevate serum BNP， IL-6， and MMP-9 levels， a reduced IL-10 level （P<0.01）， downregulated expression of CD31 and VE-cadherin， and upregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β1， and POSTN （P<0.05，P<0.01）， accompanied by increased CD31/α-SMA co-localization. Compared with the model group， the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure， increased LVEF and LVFS， decreased LVEDD and LVESD， attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition， declined serum BNP， IL-6， and MMP-9 levels， an elevated serum IL-10 level， upregulated expression of CD31 and VE-cadherin， downregulated expression of α-SMA， Col1A2， HIF-1α， TGF-β1， and POSTN， and reduced CD31/α-SMA co-localization （P<0.05，P<0.01）. No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups. ConclusionHXWTF may regulate the HIF-1α/TGF-β1/POSTN pathway to inhibit EndMT， thereby ameliorating post-MI ventricular remodeling.
