Objective:

2

To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice.

Methods:

2

A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table

66 mice were randomly divided into 6 groups (

n

=11 per group): the sham group

the model group

the LY-294002 group

the TXL group

the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling

TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was

used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry

immunofluorescence staining and flow cytometry

respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31)

α-smoth muscle actin (α-SMA)

phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot.

Results:

2

TXL improved cardiac function in MIRI mice

reduced the degree of myocardial fibrosis

increased the expression of CD31 and inhibited the expression of α-SMA

thus inhibited the occurrence of EndMT (

P

<

0.05 or

P

<

0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (

P

<

0.05 or

P

<

0.01). There was no significant difference between TXL and BNPL group (

P

>

0.05). In addition

the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention

eliminated the protective effect of TXL

further supporting the protective effect of TXL.

Conclusion:

2

TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.