Objective

2

To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1)

ferroptosis suppressor protein 1 (FSP1)

atrial natriuretic peptide (ANP)

and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF)

and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF.

Methods

2

Fifty SD rats were randomly divided into a normal group (

n

=10) and a modeling group (

n

=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling

the rats were randomly divided into a model group (

n

=9)

a moxibustion group (

n

=8)

a rapamycin (RAPA) group (

n

=9)

and a moxibustion+RAPA group (

n

=9). In the moxibustion group

moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15)

15 min at each point in each intervention

once daily

for 4 consecutive weeks. In the RAPA group

RAPA solution was administered intraperitoneally at a dose of 1 mg/kg

once daily for 4 consecutive weeks. In the moxibustion+RAPA group

RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventric

ular fractional shortening (FS) were measured after modeling and intervention. After intervention

morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1

FSP1

ANP

and CollagenⅠ in myocardial tissue.

Results

2

Compared with the normal group

the EF and FS values decreased (

P

<

0.01); necrosis

edema

degeneration

and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated

the structure of myocardial fibers was disarranged

the collagen fibers were obviously deposited and fibrosis increased (

P

<

0.01); the total iron content and the protein and mRNA expression of TfR1

ANP

and CollagenⅠ in myocardial tissue were elevated (

P

<

0.01)

while the protein and mRNA expression of FSP1 were reduced (

P

<

0.01) in the model group. Compared with the model group

the moxibustion group showed that EF and FS increased (

P

<

0.01); myocardial cell morphology was improved

and myocardial fibrosis was alleviated (

P

<

0.01); the total iron content and the protein and mRNA expression of TfR1

ANP

and CollagenⅠ in myocardial tissue decreased (

P

<

0.01)

while the protein and mRNA expression of FSP1 increased (

P

<

0.01

P

<

0.05). Compared with the model group

the myocardial fibrosis was increased (

P

<

0.05); the total iron content and the protein and mRNA expression of TfR1

ANP

CollagenⅠ in myocardial tissue were increased (

P

<

0.01)

while protein and mRNA expression of FSP1 decreased (

P

<

0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group

EF and FS were elevated (

P

<

0.01

P

<

0.05); myocardial cells were improved in morphology

the total iron content and the protein and mRNA expression of TfR1

ANP

and CollagenⅠ in myocardial tissue decreased (

P

<

0.01)

while protein and mRNA expression of FSP1 increased (

P

<

0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group

the RAPA group showed the decrease in EF and FS (

P

<

0.01)

the worsened myocardial fibrosis (

P

<

0.01)

the increase in the total iron content and the protein and mRNA expression of TfR1

ANP

and CollagenⅠ in myocardial tissue (

P

<

0.01)

and the decrease in the protein and mRNA expression of FSP1 (

P

<

0.01).

Conclusion

2

Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.