| Background The mortality rate of cardiovascular disease is much higher than that of other diseases,and the number of patients is also increasing year by year.Chronic heart failure(CHF),as the end stage of cardiovascular disease,seriously endangers the life safety of patients.Patients with heart failure are prone to suffer from psychological diseases such as anxiety and depression due to the long-term impact of the disease.Patients with heart failure and depression face a higher risk of death than ordinary patients with heart failure.As a selective serotonin reuptake inhibitor,escitalopram,an antidepressant,has been found to relieve cardiac dysfunction in patients while treating depression.As the main action link of escitalopram,5-hydroxytryptamine(5-HT)in chronic heart failure is poorly understood.Exploring the mechanism of action of drugs,giving full play to the therapeutic potential of drugs,clarifying the role of 5-HT in the course of CHF,finding new therapeutic targets,and combining basic research with clinical practice are of great significance for reducing the medical burden of patients,enriching the theory of multidisciplinary combination therapy,and improving the level of clinical diagnosis and treatment.Objective To observe the rat model of heart failure and explore the specific mechanism of escitalopram in the treatment of chronic heart failure.Methods The rat model of chronic heart failure was prepared by abdominal aortic constriction,and male SD rats were randomly divided into 7 groups: Sham group,Model group,low-dose escitalopram 1mg/kg(ESC-L)group,conventional-dose escitalopram2mg/kg(ESC-M)group,high-dose escitalopram 4mg/kg(ESC-H)group,escitalopram2mg/kg Cabaser 0.3mg/kg(ESC-M+Cabaser)group and Cabaser 0.3mg/kg(Cabaser)group.Different treatments were given according to the different groups,and Sham and Model groups were given equivalent physiological saline by gavage for 3 weeks.ESC-L,ESC-M,ESC-H,ESC-M+Cabaser,and Cabaser groups were given corresponding doses of drugs by gavage for 3 weeks.The main indicators included: rat body weight(BW),heart weight(HW),lung weight(LW)measurements,and calculation of HW/BW and LW/BW;Masson staining was used to observe myocardial fibrosis,and the fibrosis area was analyzed by Image J software;ELISA was used to detect plasma NT-pro BNP,TGF-β1,and 5-HT levels;Western Blotting was used to detect 5-HT2 B,Smad3,and Gal-3 protein expression;Fluorescence quantitative PCR was used to detect 5-HT2 B m RNA expression levels.Results 1)Compared with the Model group,the NT-pro BNP levels of ESC-L group,ESC-M group,and ESC-H group were decreased,and ESC-M group and ESC-H group were statistically different from the Model group(P<0.05).There was no significant difference between the ESC-M+Cabaser group and the Model group using the agonist.2)The myocardial fibrosis area of ESC-L group,ESC-M group,and ESC-H group was significantly lower than that of the Model group,and there was no significant difference between the ESC-M+Cabaser group and the Model group.3)The plasma 5-HT levels in the Model group were significantly higher than those in the ESC-L group,ESC-M group,and ESC-H group,and there was no significant difference between the ESC-M+Cabaser group and the Model group.4)The expression levels of 5-HT2 B receptors and 5-HT2 B m RNA in the drug-treated group(ESC-L group,ESC-M group,and ESC-H group)were lower than those in the Model group,and the changes in receptor levels were not interfered by the agonist.The ESC-M+Cabaser group was also significantly lower than the Model group(P<0.05).5)The TGF-β1 level in the drug-treated group(ESC-L group,ESC-M group,and ESC-H group)was significantly lower than that in the Model group,while there was no significant difference in the TGF-β1 level between the ESC-M+Cabaser group and the Model group.6)The drug-treated group(ESC-L group,ESC-M group,and ESC-H group)could reduce the expression level of Gal-3,and the Gal-3 level in the ESC-M+Cabaser group was lower than that in the Model group,and the result was statistically significant(P<0.05).Conclusion 1.Escitalopram participates in the regulation of heart function in rats with chronic heart failure by reducing the peripheral concentration of 5-HT.2.Escitalopram can directly reduce the expression levels of 5-HT2 B and 5-HT2 B m RNA,and inhibit myocardial fibrosis.3.5-HT regulates the TGF-β1 level by activating 5-HT2 B receptors,thus intervening in the process of myocardial fibrosis.This process may also be regulated by selective serotonin reuptake inhibitors,including escitalopram. |
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