基于中医理论构建三重打击HFpEF气虚血瘀证候模型小鼠及其评价OA

Objective To construct a mouse model of heart failure with preserved ejection fraction(HFpEF)exhibiting Qi defi-ciency and blood stasis syndrome based on traditional Chinese medicine theory and clinical characteristics,using a"triple hit"method comprising N-nitro-L-arginine methyl ester(L-NAME)administration,a high-fat diet and exhaustive exercise.Methods Forty-five male C57BL/6N mice were randomly divided into three groups based on body weight:control group,model group and syndrome group.The model group was given a high-fat diet and L-NAME in drinking water for 10 weeks.The syn-drome group received the same treatment,with an additional 4 weeks of exhaustive treadmill exercise.After the modeling period,the differences in function among the three groups were evaluated using a combination of non-invasive blood pressure measure-ment,treadmill tests,cardiac ultrasound,hemodynamic detection,non-invasive lung function tests,lung CT,mouse tongue color analysis and blood biomarker detection.Results The mice of the syndrome group showed signs of Qi deficiency such as decreased exercise capacity,small airway obstruction,prolonged end-inspiratory pause and increased lung air content(P＜0.01).Addition-ally,they exhibited signs of blood stasis,including increased body weight,elevated blood pressure,cardiac hypertrophy,slowed blood flow,hypercoagulable state,release of inflammatory factors and darker tongue color(P＜0.01,P＜0.05).These changes in functional indicators suggested the successful construction of a mouse model with Qi deficiency and blood stasis syndrome.Con-clusion The"triple hit"method effectively simulates the disease characteristics and TCM syndrome manifestations of HFpEF pa-tients with Qi deficiency and blood stasis,providing a new approach for constructing mouse models for subsequent syndrome research.