Protective and Therapeutic Effects of Chinese Medicine Formula Jiajian Yunvjian on Experimental Cardiac Remodeling after Myocardial Infarction Induced by Coronary Artery Ligation

Abstract

Introduction. This study was designed to explore the effect and mechanism of a classic Chinese medicine formula Jiajian Yunvjian (JJYNJ) on cardiac remodeling. Cardiac remodeling after myocardial infarction (MI) model was achieved by coronary artery ligation (CAL). Methodology. When dosed orally once daily, the effects of JJYNJ on hemodynamics, left ventricular weight index (LVWI), heart weight index (HWI), concentration, and gene expression of neuroendocrine factors as well as the histomorphological observation were determined. Results. After 4 weeks, mild cardiac remodeling in CAL group was characterized compared with sham group, but after 4 weeks of treatment of JJYNJ, hemodynamics improved, HWI reduced, and circulating angiotensin II (Ang II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), and hydroxyproline (Hyp) concentrations as well as Ang II receptor type 1 (AT1R) mRNA, transforming growth factor β 1 (TGF-β 1) mRNA, and TNF-α mRNA levels in myocardium were lower than in CAL group. Decreased plasma aldosterone (ALD) concentration, cross-sectional area of cardiomyocyte, collagen volume fraction (CVF), collagen types I and III, perivascular collagen area (PVCA), and upregulated nitric oxide (NO) levels were observed at the same time. Conclusions. These findings suggest that JJYNJ may have a protective and therapeutic function on cardiac remodeling related to MI.

Figure 1

Comparison of myocardium Ang II (a), ALD (b), ET-1 (c), NO (d), TNF-α (e) and Hyp (f) levels 4 weeks after coronary artery ligation in sham, CAL and JJYNJ groups. Each bar is expressed as means ± standard deviation, ^∗ p < 0.05 when compared to the sham; ^# p < 0.05 when compared to the CAL; ^§ p < 0.05 when compared to the sham.

Figure 2

Hematoxylin and eosin staining demonstrating cross-sectional area of cardiomyocyte of left ventricular tissue section from sham, CAL, and JJYNJ treated rats 4 weeks after coronary artery ligation. Each bar is expressed as means ± standard deviation; ^∗ p < 0.05 when compared to the sham; ^# p < 0.05 when compared to the CAL (magnification: ×400).

Figure 3

Representative photomicrographs (a and b) of left ventricular tissue section stained by picric Sirius red obtained from sham, CAL, and JJYNJ treated rats 4 weeks after coronary artery ligation. Relative quantitative analysis was performed for CVF (c), collagen I and collagen III (d), and PCVA (e). Each bar is expressed as means ± standard deviation; ^∗ p < 0.05 when compared to the sham; ^# p < 0.05 when compared to the CAL; ^§ p < 0.05 when compared to the sham (magnification: ×400).

Figure 4

Real time RT-PCR was performed for analyzing AT₁R mRNA (a), TGFβ ₁ mRNA (b), and TNF-α mRNA (c) expression using left ventricular tissue obtained from sham, CAL, and JJYNJ treated rats 4 weeks after coronary artery ligation. GAPDH was used as a quantitative control. Each bar is expressed as means; ^∗ p < 0.05 when compared to the sham; ^# p < 0.05 when compared to the CAL; ^§ p < 0.05 when compared to the sham.