Objective

2

Based on the "five elements theory"， to explore the differences in cardiac structure and function between age-matched heart failure mice in winter and summer， as well as the differences in the therapeutic effects of Linggui Zhugan （LGZG） Decoction， which is a representative formula for warming yang and promoting diuresis， thereby providing a scientific basis for the "five elements theory".

Methods

2

Twenty-six C57BL/6J mice were included in the summer batch， and 22 in the winter batch. Mice in each seasonal batch were randomly divided into summer/winter sham operation groups， summer/winter model groups， and summer/winter traditional Chinese medicine （TCM） groups. Chronic heart failure （CHF） mouse model were established by continuous administration of isoproterenol （ISO） at a dose of 40 mg·kg⁻¹·d⁻¹ via osmotic minipumps for 14 days. Mice in the summer/winter TCM groups were gavaged with LGZG Decoction （2.4 g·kg⁻¹）， while those in the summer/winter sham operation groups and summer/winter model groups were gavaged with an equal volume of 0.9% NaCl solution， with the intervention lasting for 4 weeks. Cardiac structure and function were assessed using small animal echocardiography. The degree of myocardial hypertrophy was evaluated by the heart weight/body weight （HW/BW） and heart weight/tibia length （HW/TL）； the severity of heart failure was measured by the lung weight/body weight （LW/BW） and lung weight/tibia length （LW/TL）. Hematoxylin-eosin （HE） staining， Sirius Red staining， and Masson staining were used to observe histopathological changes in myocardial tissue structure.

Results

2

①There were no significant differences in the changes in HW/BW， HW/TL， LW/BW， and LW/TL between the winter model group and the summer model group（

P

>

0.05）； there were no significant differences in these changes after treatment with LGZG Decoction（

P

>

0.05）. ②The amplitude of change in the left ventricular posterior wall thickness in systole （LVPWs） in the wint

er model group mice was significantly greater than that in the summer model group （

P

<

0.05）， and the amplitude of change in the left ventricular internal diameter in systole （LVIDs） was significantly greater in the winter model group mice than that in the summer model group （

P

<

0.05）. After treatment with LGZG Decoction， The amplitude of change in interventricular septal thickness in systole （IVSs） and LVPWs of mice in the winter TCM group were significantly greater than those in the summer TCM group （

P

<

0.05）. ③The amplitude of change in the left ventricular ejection fraction （EF） and left ventricular fractional shortening （FS） of mice in the winter model group were significantly greater than those in the summer model group （

P

<

0.05）. After treatment with LGZG Decoction， the increases in EF and FS in the winter TCM group were significantly greater than those in the summer TCM group （

P

<

0.05）. ④HE staining showed that cardiomyocyte disarray and hypertrophy were more severe in the winter model group， and myocardial structure recovery was more obvious in the winter TCM group after intervention with LGZG Decoction. Sirius Red and Masson staining showed no significant seasonal differences in myocardial fibrosis.

Conclusions

2

Based on the theory of over-restraint and counter-restraint in the five elements， the cardiac function of CHF model mice is worse in winter， meaning they "tolerate summer but not winter". In syndrome differentiation and treatment， LGZG Decoction， the representative formula for warming yang and promoting diuresis， is more syndrome-appropriate in winter， thus achieving better therapeutic effects.