Establishment and Evaluation of Animal Model of Acute Myocardial Infarction with Syndrome of Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Pathogenesis of Metabolic Remodeling of Energy Substrate Based on Theory of Deficient Qi Stagnation and Progress of Chinese Medicine Intervention / 中国实验方剂学杂志

In the case of cardiac dysfunction， energy metabolism changes and the metabolism of myocardial substrates is reconstructed， as manifested by variation in the selection and utilization of energy substrates such as fatty acids and glucose. Persistent metabolic disorders of substrates will decrease energy supply， thus resulting in the occurrence and development of heart failure. Metabolic remodeling of substrate is resulted from the decline of visceral function and the accumulation of pathological products. Deficient Qi stagnation is the core pathogenesis. Deficient Qi （heart Qi deficiency， insufficient energy） is the root cause， which exists in the whole disease course. Stagnation （phlegm， blood stasis， fluid， lipid toxic products， lactic acid， etc.） is the symptom， which evidences the aggravation of the disease. Deficient Qi and stagnation are intertwined and causal， which form a spiral vicious circle. The typical syndrome is excess resulted from deficiency and deficiency-excess in complexity. The treatment principle is reinforcing healthy Qi and tonifying deficiency， dredging and removing pathogen. At the early stage， the method of reinforcing healthy Qi and tonifying deficiency （benefiting Qi） should be used， and the method of dredging and removing pathogen （activating blood） can be applied according to the conditions of patients. At the middle and late stages， both reinforcing healthy Qi and tonifying deficiency （benefiting Qi and warming Yang） and dredging and removing pathogen （activating blood， resolving stasis， and excreting water） should be emphasized. Chinese medicine can be applied according to the pathogenesis， thereby promoting the utilization of fatty acids， glucose， and other substrates and reducing the accumulation of toxic products derived from metabolic remodeling of substrate. Thus， both the root cause and symptoms can be alleviated， further improving cardiac energy metabolism and heart function.