Exploration Of The Clinical And Basic Research Of Qihong Capsule In Regulating Myocardial Energy Metabolism In Chronic Heart Failure Based On The Theory Of Phlegm And Blood Stasis

Objective:(1)To explore the pathogenesis of chronic heart failure(CHF)and provide new insights into the prevention and treatment of CHF through Traditional Chinese Medicine using the theory of phlegm and blood stasis;(2)To investigate the effectiveness and safety of Qihong Capsule in treating CHF,offering new methods for the prevention and treatment of CHF with traditional Chinese medicine(TCM);(3)To investigate the intervention effects of Qihong Capsule on myocardial energy metabolism remodeling and the mitochondrial DNA-cGAS-STING signaling pathway in CHF rats,providing theoretical guidance and experimental basis for the prevention and treatment of CHF with Qihong Capsule.Methods:(1)Classical Chinese medical literature and books related to the theory of phlegm and blood stasis were systematically reviewed,research findings on the theory of phlegm and blood stasis both domestically and internationally were comprehensively reviewed,the connotations of the theory of phlegm and blood stasis were elucidated,the theory of phlegm and blood stasis was applied to understand CHF,and its pathogenesis and prevention and treatment methods were explored.(2)From May 2022 to September 2023,patients with CHF from the outpatient and inpatient departments of the Fourth Clinical Medical College of Xinjiang Medical University were selected.A randomized,controlled,standard treatment-loaded clinical research design was adopted,and patients were divided into control and experimental groups.The control group received standardized Western medicine treatment,while the experimentalgroup received standardized Western medicine treatment plus Qihong Capsule treatment,for a total of 12 weeks.Main efficacy evaluation indicators are 6-minute walk test(6MWT)and N-terminal probrain natriuretic peptide(NT-pro BNP).Secondary efficacy evaluation indicators include NYHA functional classification,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVED),Minnesota Living with Heart Failure Questionnaire(MLHFQ),and Traditional Chinese Medicine Syndrome Score(TCM-SS).Safety evaluation indicators involve vital signs,physical examination,blood routine,urine routine,liver and kidney function,electrolytes,twelve-lead electrocardiogram,adverse events,adverse reactions,etc.(3)(1)The thoracic aortic constriction method was used to establish a rat model of CHF,and it was divided into sham surgery group,CHF model group,Qihong Capsule low-dose group,Qihong Capsule medium-dose group,Qihong Capsule high-dose group,and quinapril group.Intervention treatments,including low,medium,and high doses of Qihong Capsule and quinapril,were used;(2)The myocardial tissue morphology under the microscope after Masson staining,the ultrastructure of myocardial cells under transmission electron microscopy,and the effects of Qihong Capsule on the heart function and myocardial structure of CHF rats were observed;(3)Serum L-lactic acid(L-LA),free fatty acids(FFA),glucose(Glu),ketone bodies,ATP,superoxide dismutase(SOD)activity,malondialdehyde(MDA),and protein carbonyl content were detected to evaluate the effects of Qihong Capsule on myocardial energy metabolism substrates;(4)The content of reactive oxygen species(ROS)and mitochondrial DNA(mt DNA)protein expression levels in myocardial tissue were detected,the effects of Qihong Capsule on oxidative stress in CHF and its protective effect on mt DNA were evaluated;(5)The m RNA and protein expression levels of key factors in the cGAS-STING signaling pathway in CHF rat myocardial tissue were detected,and the key role of Qihong Capsule in regulating myocardial energy metabolism in CHF were evaluated.Results:(1)Exploration of the origin of using phlegm and blood stasis-related theory to diagnose and treat CHF and provide new insights into the prevention and treatment of CHF:(1)Dysfunction of Organ Qi and blood circulation disorders are the key causes leading to the pathological production of phlegm and stasis in CHF.The mutual formation of phlegm and stasis is the main pathogenesis,and phlegm and stasis are the key nodes in the evolution of the etiology and pathogenesis of CHF.The simultaneous treatment of phlegm and stasis and the support of the right and elimination of evil are important therapeutic principles.(2)Relevant basic and clinical research also shows that the simultaneous treatment of phlegm and stasis can intervene in the myocardial energy metabolism process of heart failure,regulate oxidative stress,protect mitochondria,and improve cardiac function.The simultaneous treatment of phlegm and stasis is an effective method for diagnosing and treating CHF.(2)Clinical study on the effectiveness and safety of Qihong Capsule in the treatment of CHF:(1)After treatment,the distance covered in the 6MWT increased in the experimental group(P<0.05).The proportion of increased distance in the 6MWT in the experimental group(87.30%)was higher than that in the control group(56.72%)(P<0.001).After treatment,the NT-pro BNP level decreased in the experimental group(P<0.05).The proportion of decreased NT-pro BNP in the experimental group(73.02%)was higher than that in the control group(38.81%)(P<0.001).(2)After treatment,the LVEF increased in the experimental group(P<0.05).The MLHFQ score decreased in the experimental group(P<0.05).The proportion of decreased MLHFQ score in the experimental group(93.65%)was higher than that in the control group(59.70%)(P<0.001).The proportion of decreased TCM-SS score in the experimental group(93.65%)was higher than that in the control group(73.13%)(P<0.01).The total effective rate of TCM syndrome in the experimental group(66.66%)was higher than that in the control group(38.81%)(P<0.05).(3)Stratified analysis was conducted based on LVEF≥50% and LVEF<50%:(A)Comparisons of the results after treatment in patients with LVEF<50%: a.After treatment,the distance covered in the 6MWT increased in the experimental group(P<0.05).The proportion of increased distance in the 6MWT in the experimental group(91.18%)was higher than that in the control group(51.52%)(P<0.05).b.After treatment,the NT-pro BNP level decreased in the experimental group(P<0.05),and the proportion of decreased NT-pro BNP in the experimental group(91.18%)was higher than that in the control group(51.52%)(P<0.05).c.After treatment,the proportion of improvement in NYHA functional class III-IV in the experimental group(32.35%)was lower than that in the control group(66.67%)(P<0.05).d.After treatment,the proportion of decreased MLHFQ score in the experimental group(94.12%)was higher than that in the control group(57.58%)(P<0.05).e.There was no statistically significant difference in the total effective rate between the experimental group and the control group(P>0.05).(B)Comparisons of the results after treatment in patients with LVEF≥50%: a.After treatment,the distance covered in the 6MWT increased in the experimental group(P<0.05),and the proportion of increased distance in the 6MWT in the experimental group(82.76%)was higher than that in the control group(61.76%)(P<0.05).b.After treatment,the NT-pro BNP level decreased in the experimental group(P<0.05),and the proportion of decreased NT-pro BNP in the experimental group(72.41%)was higher than that in the control group(47.06%)(P<0.05).c.After treatment,the proportion of decreased MLHFQ score in the experimental group(93.10%)was higher than that in the control group(61.76%)(P<0.05).d.After treatment,the proportion of decreased TCM-SS score in the experimental group(96.55%)was higher than that in the control group(70.59%)(P<0.05).e.The total effective rate of TCM syndrome in the experimental group(72.41%)was higher than that in the control group(41.18%)(P<0.05);(4)Safety evaluation: There were no significant differences in vital signs,physical examination,blood routine,liver and kidney function,electrolytes,urine routine,or electrocardiogram between the experimental group and the control group after treatment(P>0.05).Furthermore,no serious adverse events or adverse reactions occurred,indicating good safety.(3)The intervention effect of Qihong Capsule on myocardial energy metabolism in rats with CHF:(1)The intervention of Qihong Capsule on myocardial energy metabolism reconstruction had effects on the cardiac function and myocardial tissue morphology of rats with CHF: Compared with the CMD group,the middle and high dose groups of Qihong Capsule increased the LVEF(P<0.01),alleviated pathological damage to myocardial tissue in CHF rats,significantly reduced the fiber content in myocardial tissue(P<0.001),and markedly improved mitochondrial ultrastructural damage;(2)The effect of Qihong Capsule on serum metabolic substrates in rats with CHF: Compared with the CMD group,all doses of Qihong Capsule could reduce the expression of L-lactic acid(L-LA)and FFA and increase ketone body levels(P<0.01);the high-dose Qihong Capsule group could provide more ATP for myocardium,increase SOD activity(P<0.01),and reduce protein carbonyl expression levels(P<0.001);(3)The effect of Qihong Capsule on the mt DNA-cGAS-STING signaling pathway: Compared with the CMD group,all doses of Qihong Capsule could decrease the expression of ROS and mitochondrial DNA(mt DNA)(P<0.001,P<0.0001)and inhibit the gene expression of cGAS and STING on the cGAS-STING signaling pathway(P<0.0001).Conclusion:(1)Viewing CHF through the lens of phlegm and blood stasis-related theory,dysfunction of organ qi and blood circulation disorders are the key causes leading to the pathological production of phlegm and stasis in CHF.The mutual formation of phlegm and stasis is the main pathogenesis,and the principle of simultaneously treating phlegm and stasis while supporting the righteous and dispelling the pathogenic factors is crucial.The simultaneous treatment of phlegm and stasis has an effect on intervening in CHF myocardial energy metabolism.(2)Qihong Capsule can reduce the NT-pro BNP levels in CHF patients,improve cardiac function,increase the distance covered in the 6MWT,enhance exercise tolerance,improve quality of life and TCM clinical symptoms,and can slow the progression of CHF.It exhibits significant advantages in clinical efficacy in CHF patients with LVEF≥50%.(3)Qihong Capsule reduces the production of ROS and alleviates mt DNA damage by adjusting myocardial energy metabolism substrates,restoring myocardial energy supply,reducing myocardial fibrosis,inhibiting the cGAS-STING signaling pathway,promoting myocardial cell survival,and thereby improving cardiac function.