1.Discussion on the Scientific Connotation of"Reinforcing Yang from Yin"Method in the Treatment of Chronic Heart Failure Based on Mitochondrial Energy Metabolism
Fei WANG ; Senjie ZHONG ; Xinchun LI ; Kun LIAN ; Lin LI ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):6-10
Chronic heart failure is the final stage of various cardiovascular diseases,and mitochondrial energy metabolism disorders have been proved to play an important role in the development of chronic heart failure.TCM believes that heart yin is the material basis of heart yang(qi),and deficiency of heart yang(qi)is the core pathogenesis of chronic heart failure.Based on mitochondrial energy metabolism,this article expounded the scientific connotation of"reinforcing yang from yin"in the treatment of chronic heart failure from the aspects of theoretical connotation,pathogenesis,pathophysiological relationship and modern research.In-depth study at the microscopic level demonstrated that the application of"reinforcing yang from yin"method can effectively improve the reconstruction of heart energy substrate(yin),enhance mitochondrial function,and finally provide energy support(yang),which could offer ideas for theoretical research and clinical prevention and treatment of chronic heart failure.
2.Comparison of different regimens in isoprenaline-induced chronic heart failure models
Yuquan TAN ; Junyu ZHANG ; Meng YANG ; Fei WANG ; Senjie ZHONG ; Lin LI ; Zhixi HU
Acta Laboratorium Animalis Scientia Sinica 2024;32(2):161-167
Objective To compare animal models of chronic heart failure(CHF)prepared by three different protocols,to establish a stable,reliable,and reproducible mouse model of CHF.Methods Twenty-five male C57BL/6J mice were divided randomly into four groups:a blank group,model A group(MA group),model B group(MB group),and model C group(MC group).The model groups adopted different preparation protocols for continuous injection of isoprenaline.The MA group and MB group were dose-decreasing models:MA group:subcutaneous injection of 10 mg/kg on day 1,5 mg/kg on day 2,2.5 mg/(kg·d)on days 3~30,total 30 days;and MB group:subcutaneous injection of 20 mg/kg on day 1,10 mg/kg on day 2,5 mg/(kg·d)on days 3~14,total 14 days.The MC group used a constant dose of intraperitoneal injection of 7.5 mg/(kg·d)for 28 days.The day after the final injection,the survival and model-formation rates for each group of mice were calculated.Cardiac function was measured by cardiac ultrasound and serum levels of N-terminal pro B-type natriuretic peptide,interleukin-6,and tumor necrosis factor-α were measured.Results CHF was successfully induced in all the model groups after all injections at the end of the fourth week.However,comprehensive test result showed that the MC model was the most stable.Conclusions An isoprenaline-induced mouse model of CHF using constant intraperitoneal injection of 7.5 mg/(kg·d)for 28 days may be the most suitable model for subsequent research on traditional Chinese medicine.
3.Pathogenesis of Metabolic Remodeling of Energy Substrate Based on Theory of Deficient Qi Stagnation and Progress of Chinese Medicine Intervention
Jing LI ; Senjie ZHONG ; Huifang KUANG ; Yang YANG ; Yi LIU ; Shuchun HUANG ; Zhihua GUO ; Qiuyan ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):195-202
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.
4.Based on Theory of "Deficiency of Qi and Stagnation" to Explore Pathogenesis of Chronic Renal Failure "Micro-inflammatory State" and Progress of Traditional Chinese Medicine Prevention and Treatment
Meng YANG ; Siyuan HU ; Lin LI ; Senjie ZHONG ; Ziyi WANG ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):229-235
Chronic renal failure (CRF) is generally characterized by micro-inflammatory state, which can aggravate the CRF process in severe cases, leading to the deterioration of renal function, malnutrition, anemia and other complications. Therefore, it is of great significance to improve the micro-inflammatory state of CRF. "Deficiency of Qi and stagnation" is the basic pathogenesis of the micro-inflammatory state of CRF, which runs through the whole process of the disease and affects the formation and outcome of CRF in different forms. Traditional Chinese medicine (TCM) has unique advantages in improving the micro-inflammatory state and enhancing the immunity of the body due to its advantages of syndrome differentiation and treatment, strengthening the righteousness and eliminating pathogenic factors. Therefore, the author systematically sorted out the relationship between micro-inflammatory state and CRF, understanding of micro-inflammatory state of CRF and its prevention and treatment of TCM by referring to relevant literature, based on the theory of "deficiency of Qi and stagnation", and proposed that spleen and kidney failure (deficiency of Qi) is the origin of micro-inflammatory state of CRF, and blood stasis and poisonous evil (stagnation) is the target of its onset. Deficiency of Qi and stagnation adhered to each other, acted as cause and effect, and developed in a spiral manner throughout the development of the disease. TCM has the effects of nourishing the spleen and kidney, removing blood stasis and turbidity. By down-regulating C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and other micro-inflammatory indicators, it can eliminate the pathological wastes derived from spleen and kidney deficiency, reduce the micro-inflammatory state, restore the balance of Yin and Yang in the body to achieve the purpose of eliminating pathogens and protecting renal function, providing guidance for the clinical treatment of CRF.
5.Study on Metabonomics of Myocardial Tissue of Rat Model with Coronary Heart Disease of Heart Blood Stasis Syndrome
Jing LI ; Zhihua GUO ; Jianhe LIU ; Senjie ZHONG ; Huifang KUANG ; Yang YANG ; Yi LIU ; Qiuyan ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):119-126
Objective To investigate the biological basis of disease and syndrome by studying the spectrum of myocardial tissue metabolites in the rat model of coronary heart disease with heart blood stasis syndrome.Methods SD rats were randomly divided into sham-operation group and model group.The left anterior descending coronary artery was ligated to prepare the rat model of coronary heart disease with heart blood stasis syndrome.The general condition was observed,and the tongue chromaticity,electrocardiogram,cardiac function were detected.HE staining and transmission electron microscopy were used to observe myocardial tissue morphology and ultrastructure.UPLC-MS technology was used to investigate the differential metabolites in rat myocardial tissue,and enrichment analysis was conducted on metabolic pathways.Results Compared with the sham-operation group,the tongue chromaticity R,G,B values of model group rats were significantly reduced(P<0.05),ECG heart rate and ST segment elevation amplitude significantly increased(P<0.05),LVEF and LVFS significantly decreased,and LVIDs and LVIDd significantly increased(P<0.05).Myocardial tissue pathology revealed that the structure was blurred,inflammatory cells infiltrated,mitochondria swelled,ruptured,and dissolved,and crista structure fracture decreased.A total of 29 potential biomarkers with significant differences between the sham-operation group and the model group were identified in metabolomics(7 upregulated and 22 downregulated),with the majority of 10 pathways enriched in thiamine metabolism,arginine biosynthesis,purine metabolism,aminoacyl-tRNA biosynthesis,alanine,aspartate and glutamate metabolism,pentose and glucuronate interconversions,glycolysis/gluconeogenesis,valine,leucine and isoleucine degradation,TCA cycle,pyruvate metabolism.Conclusion Ligation of the left anterior descending coronary artery can mimic the pathological process of coronary heart disease with blood stasis syndrome in a good way,and its pathological mechanism involves the disruption of multi-level metabolic networks such as glucose metabolism,mitochondrial energy metabolism,amino acid metabolism,protein biosynthesis,and purine metabolism.
6.Exploration on Syndrome Types and Metabolic Markers of Rat Model with Heart Failure Caused by Transverse Aortic Constriction Based on Theory of Correspondence of Prescription and Syndrome
Senjie ZHONG ; Xiajun XIONG ; Qian ZHANG ; Siyuan HU ; Meng YANG ; Shumin HUANG ; Ge FANG ; Ziyi WANG ; Lin LI ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):130-139
ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine (TCM) injections on rat model of heart failure induced by transverse aortic constriction (TAC), explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome, and reveal the biological basis of prescription-syndrome from the perspective of metabolism. MethodRats were treated with TAC for modeling and were divided into Shenmai injection group (6.0 mL·kg-1), model group, Danhong injection group (6.0 mL·kg-1), Shenfu injection group (6.0 mL·kg-1) and trimetazidine group (10 mg·kg-1), and sham operation group was set up as control. After drug intervention for 15 days, echocardiography, serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and myocardial histopathological staining were performed for each group, so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection, and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue. ResultCompared with the sham operation group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (FS) in the model group decreased (P<0.01), while the left ventricular end-diastolic diameter (LVIDd), left ventricular internal diameter at end-systole (LVIDs) and NT-proBNP level increased (P<0.01). Compared with model group, LVEF and FS increased (P<0.01), LVIDd, LVIDs and NT-proBNP level decreased (P<0.05, P<0.01) in Danhong injection group, NT-proBNP level in Shenfu injection group decreased (P<0.05), LVIDd and NT-proBNP level increased (P<0.05, P<0.01) in Shenmai injection group, in trimetazidine group, LVEF and FS increased (P<0.01), while LVIDs and NT-proBNP level decreased (P<0.05, P<0.01). Serum glucose, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks (P<0.01, P<0.05). There were the callback of 9 myocardial metabolites in Danhong injection group, including glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group, including glycerol phospholipid metabolism. ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection, suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid, glucose, amino acid and butyric acid.