Objective

2

Based on the classic traditional Chinese medicine （TCM） theory of "Yougu Wuyun （existing defects without causing fatality）"， the study aimed to explore the different effects of Fuzi （Aconiti Lateralis Radix Praeparata） decoction on the heart of both healthy and chronic heart failure mice.

Methods

2

Eight-week-old male SPF C57BL/6J mice were randomly divided into control group （Ctrl）， Fuzi group （FZH）， doxorubicin group （Dox）， and doxorubicin plus Fuzi group （Dox+FZH）. Mice in Dox and Dox+FZH groups received intraperitoneal injections of 5 mg/kg doxorubicin every 3 days. Mice in Ctrl and FZH groups received equivalent volumes of saline （9 g/L） intraperitoneally. On the first day of the experiment， mice in Dox and Dox+FZH groups received intraperitoneal injections of 5 mg/kg doxorubicin， followed by daily gavage with 2 g/kg Fuzi Decoction for mice in FZH and Dox+FZH groups. Mice in Ctrl and Dox groups were gavaged with an equivalent volume of normal saline solution （9 g/L）. The modeling period lasted for 4 weeks. The general condition of the mice was observed， and survival rate， heart weight， body weight， heart weight ratio， heart-to-tibia length ratio， and echocardiographic parameters were statistically analyzed. The levels of brain natriuretic peptide （BNP） and cardiac troponin I （cTnI） in cardiac tissue and serum of mice were measured. Apoptosis-related protein expression in heart tissue was detected， and the cross-sectional area of individual cardiomyocytes was observed to assess the effects of Fuzi on myocardial injury in healthy and chronic heart failure mice.

Results

2

①In a healthy state， mice in Ctrl and FZH groups had shiny fur， proportional body shape， and normal limb movement， with no deaths observed in either group. Compared with mice in Ctrl group， mice in FZH group showed a decrease in heart weight， heart weight ratio， heart-to-tibia length ratio， left ventricular ejection fraction， left ventricular fractional shortening， heart rate， and systolic left ventricular posterior wall thickness （

P

<

0.05）， along with an increase in left ventricular end-diastolic diameter （

P

<

0.05）. Mice in FZH group showed higher Cleaved-caspase3 protein expression （

P

<

0.05）， and lower Bcl2/Bax ratio （

P

<

0.05） than mice in Ctrl group. There was no significant difference in serum BNP and cTnI levels （

P

>

0.05）. The cross-sectional area of individual cardiomyocytes in heart tissue slices was significantly reduced in FZH group mice （

P

<

0.05）.

ANP

gene expression in FZH group mice was higher than that in Ctrl group mice （

P

<

0.05）. ②In a chronic heart failure state， mice in Dox group had dull fur， were emaciated， showed slow activity， and had reduced food intake， while mice in Dox+FZH group showed improved activity and food intake compared with mice in Dox group. There were 6 deaths in Dox group and 3 deaths in Dox+FZH group. Fuzi improved the survival rate of mic

e in pathological states， but the difference was not statistically significant （

P

>

0.05）. Compared with mice in Dox group， mice in Dox+FZH group had a decrease in heart rates （

P

<

0.05） and a slight increase in left ventricular ejection fraction， but not statistically significant （

P

>

0.05）. The Bcl2/Bax ratio was significantly higher （

P

<

0.05） and Cleaved-Caspase3 protein expression was lower in Dox+FZH group mice than in Dox group mice， but not statistically significant （

P

>

0.05）. Serum BNP and cTnI levels were reduced （

P

<

0.05）， and the cross-sectional area of individual cardiomyocytes in heart tissue slices was enlarged in Dox+FZH group mice （

P

<

0.05）. There was no significant difference in

ANP

gene expression between Dox group mice and Dox+FZH group mice （

P

>

0.05）.

Conclusion

2

Fuzi has toxic effects on the heart of healthy mice， but has certain therapeutic effects on mice with chronic heart failure.