Objective:

2

To explore whether

Panax notoginseng saponins

(PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved.

Methods:

2

MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water

n

=9)

MI group (distilled water

n

=9)

PNS group (PNS

40 mg/kg daily

n

=9) and fosinopril group (FIP

1.2 mg/kg daily

n

=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP)

tumor necrosis factor α (TNF-α)

growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3)

mitogen-activated protein kinase kinase 3 (MAP2K3)

p38 mitogen-activated protein kinase (p38 MAPK)

phosphorylation of p38 MAPK (p-p38 MAPK)

transforming growth factor-β (TGF-β1)

collagen Ⅰ

nuclear factor kappa B p65 (NFκB p65)

phosphorylation of NFκB p65 (p-NFκB p65)

and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining

respectively.

Results:

2

PNS improved cardiac function and fibrosis in MI rats (

P

<

0.05). The serum levels of CRP

TNF-α

GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1

collagen Ⅰ

MAP2K3

p38 MAPK

p-p38 MAPK

NFκB p65

p-NFκB p65

and p-IκBα were down-regulated

while ATF3 increased with the treatment of PNS (

P

<

0.05).

Conclusions:

2

PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.