【摘要】 目的 基于“五行学说”探讨冬夏两季同龄心力衰竭小鼠心脏结构和功能差异以及温阳利水代表方苓桂术甘汤治疗效果差异，为“五行学说”提供科学依据。方法 C57BL/6J小鼠夏季批次26只，冬季批次22只，分别按季节随机分为夏季/冬季假手术组、夏季/冬季模型组、夏季/冬季中药组。采用微渗透泵以40 mg·kg^-1·d^-1剂量持续给予异丙肾上腺素（ISO）14 d制备慢性心力衰竭（CHF）小鼠模型。其中夏季/冬季中药组小鼠灌胃苓桂术甘汤(2.4 g·kg^-1)，夏季/冬季假手术组、夏季/冬季模型组小鼠给予等量的0.9%氯化钠溶液灌胃，共干预4周。采用小动物心脏超声观察小鼠心脏结构和功能改变；采用心质量/体质量（HW/BW）和心质量/胫骨长（HW/TL）变化幅度衡量心肌肥大情况，肺质量/体质量（LW/BW）和肺质量/胫骨长（LW/TL）的变化幅度衡量心力衰竭情况；采用苏木精-伊红（HE）染色、天狼猩红和马松（Masson）染色观察心肌组织结构改变。结果 （1）冬季模型组小鼠HW/BW、HW/TL、LW/BW、LW/TL变化幅度与夏季模型组相比无显著差异（P>0.05）；苓桂术甘汤治疗后变化幅度无显著差异（P>0.05）。（2）冬季模型组小鼠心脏的收缩期左室后壁厚度（LVPWs）变化幅度显著大于夏季模型组小鼠（P<0.05），冬季模型组小鼠心脏的收缩期左心室内径（LVIDs）变化幅度显著大于夏季模型组（P<0.05）；苓桂术甘汤治疗后冬季中药组小鼠收缩期室间隔厚度（IVSs）和LVPWs变化幅度显著大于夏季中药组（P<0.05）。（3）冬季模型组小鼠的心脏功能左心室射血分数（EF）和左心室缩短分数（FS）变化幅度显著大于夏季模型组（P<0.05）；苓桂术甘汤治疗后冬季中药组小鼠EF和FS提高均显著大于夏季中药组（P<0.05）。（4）HE染色显示，冬季模型组小鼠心肌细胞紊乱更加严重、肥大更加明显，苓桂术甘汤干预后冬季中药组心肌结构恢复更加明显；Masson和天狼猩红染色显示纤维化情况在冬、夏季节无显著差异。结论 基于五行乘侮理论，冬季CHF模型小鼠心脏功能更差，即耐夏不耐冬；辨证论治采用温阳利水代表方苓桂术甘汤在冬季的治疗更加对证，因此疗效更佳。更多还原

【Abstract】 Objective 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 Twentysix C57 BL/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(1) There 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).(2)The amplitude of change in the left ventricular posterior wall thickness in systole(LVPWs) in the winter 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).(3)The 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).(4)HE 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 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.更多还原