Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction

Abstract

Background: Paeoniflorin (PF) is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI).

Materials and methods: In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF) was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) interleukin-10 (IL-10) and brain natriuretic peptide (BNP). Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9.

Results: Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of Caspase-3 and Caspase-9 was inhibited, and apoptosis was obviously reduced in the PF treatment groups. BNP, TNF-α and IL-6 were also decreased and IL-10 was increased in the treated rats.

Conclusion: PF could significantly improve the LVEF of rats. It decreased adverse left ventricular remodeling after myocardial infarction in rat models. The potential mechanism could be that PF decreased and inhibited BNP, TNF-α and IL-6, increased IL-10 and further inhibited the expression of Caspase-3 and Caspase-9, thus promoting ventricular remodeling.

Keywords: Caspase-3; Caspase-9; myocardial infarction; paeoniflorin; ventricular remodeling.

Figure 1

The body weight of rats $\left(\overline{x}\pm \mathrm{s}\right)$ (n=15/group).

Figure 2

Effect of PF on LVWI in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$. Notes: **P<0.01, n=15/group, versus sham-operated control; ^#P<0.05, ^##P<0.01, n=15/group, versus model control. Abbreviations: LVWI, left ventricle weight index; PF, paeoniflorin.

Figure 3

Effect of PF on cardiac function in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$. Note: (A) HR, (B) LVEF, (C) LVIDd and (D) LVIDs. **P<0.01, n=15/group, versus sham-operated control, ^#P<0.05, ^##P<0.01, n=15/group, versus model control. Abbreviations: HR, heart rate; LVEF, left ventricular ejection fraction; LVIDd, left ventricular end-diastolic inner diameter; LVIDs, left ventricular end-systolic inner diameter; PF, paeoniflorin.

Figure 4

HE staining results. Notes: Effect of PF on heart histopathology in rats with myocardial infarction (HE, ×200): (A) sham-operated control; (B) model control; (C) captopril group; (D) low-dose group; (E) middle dose group and (F) high-dose group. Abbreviation: PF, paeoniflorin.

Figure 5

Effect of PF on heart histopathology in rats with myocardial infarction (Masson staining, ×200): (A) sham-operated control; (B) model control; (C) captopril group; (D) low-dose group; (E) middle dose group; (F) high-dose group and (G) fibrosis (%). Notes: **P<0.01, n=15/group, versus sham-operated control; ^##P<0.01, n=15/group, versus model control. Abbreviation: PF, paeoniflorin.

Figure 6

Effect of PF on myocardial mitochondria in rats with myocardial infarction (transmission electron microscope, ×20,000). Note: (A) Sham-operated control; (B) model control; (C) captopril group; (D) low-dose group; (E) middle dose group and (F) high-dose group. Abbreviation: PF, paeoniflorin.

Figure 7

Effect of PF on apoptosis in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$; TUNEL, ×200): (A) sham-operated control; (B) model control; (C) captopril group; (D) low-dose group; (E) middle dose group; (F) high-dose group and (G) AI (%). Notes: **P<0.01, n=15/group, versus sham-operated control; ^##P<0.01, n=15/group, versus model control. Abbreviations: AI, apoptosis index; PF, paeoniflorin; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Figure 8

Effects of PF on the levels of BNP, TNF-α, IL-6 and IL-10 in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$. Note: (A) BNP, (B) TNF-α, (C) IL-6 and (D) IL-10; **P<0.01, n=15/group, versus sham-operated control; ^#P<0.05, ^##P<0.01, n=15/group, versus model control. Abbreviations: BNP, brain natriuretic peptide; IL-6, interleukin-6; IL-10, interleukin-10; PF, paeoniflorin; TNF-α, tumor necrosis factor-α.

Figure 9

Effects of the PF on the expression of Caspase-3 and Caspase-9 (IOD) in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$. Notes: (A) Caspase-3, (B) Caspase-9. **P<0.01, n=15/group, versus sham-operated control, ^##P<0.01, n=15/group, versus model control. Abbreviations: IOD, integrated optical density; PF, paeoniflorin.

Figure 10

Expression of PF on the expression of Caspase-3 in myocardial cells by immunohistochemistry (inverted microscope, ×200). Note: (A) Sham-operated control, (B) model control, (C) captopril group, (D) low-dose group, (E) middle dose group and (F) high-dose group. Abbreviation: PF, paeoniflorin.

Figure 11

Effect of the PF on the expression of Caspase-9 in rats with myocardial infarction (immunohistochemistry, ×200). Note: (A) Sham-operated control, (B) model control, (C) captopril group, (D) low-dose group, (E) middle dose group and (F) high-dose group. Abbreviation: PF, paeoniflorin.

Figure 12

Effect of the PF on the expression of Caspase-3 and Caspase-9 in rats with myocardial infarction (Western blot). Note: (A) Sham-operated control, (B) model control, (C) captopril group, (D) low-dose group, (E) middle dose group and (F) high-dose group. Abbreviation: PF, paeoniflorin.

Figure 13

Effects of PF on the expression of Caspase-3 and Caspase-9 in rats with myocardial infarction $\left(\overline{x}\pm \mathrm{s}\right)$: (A) Caspase-3/β-actin; (B) Caspase-9/β-actin. Note: **P<0.01, n=15/group, versus sham-operated control, ^##P<0.01, n=15/group, versus model control. Abbreviation: PF, paeoniflorin.