Therapeutic effect of QiShenYiQi Dripping Pills on mice with heart failure with preserved ejection fraction
10.16438/j.0513-4870.2024-0599
- VernacularTitle:芪参益气滴丸对射血分数保留型心力衰竭小鼠的治疗作用
- Author:
Zhen-zhen ZHANG
1
;
Meng-yao WANG
1
;
Yan-lu HAN
1
;
Yun-hui HU
2
;
Xiao-qiang LI
2
;
Kai-min GUO
2
;
Ya-jun DUAN
3
;
Shuang ZHANG
1
Author Information
1. School of Food and Biological Engineering, Hefei University of Technology, Hefei
2. Tasly Pharmaceutical Group Co., Ltd., Tianjin Tasly Digital Intelligence Chinese Medicine Development Co., Ltd., Tianjin
3. The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei
- Publication Type:Research Article
- Keywords:
heart failure with preserved ejection fraction;
QiShenYiQi Dripping Pills;
empagliflozine;
transcriptome sequencing;
calsequestrin 1
- From:
Acta Pharmaceutica Sinica
2024;59(11):3094-3103
- CountryChina
- Language:Chinese
-
Abstract:
Heart failure with preserved ejection fraction (HFpEF) accounts for about half of the number of patients with heart failure. In addition to the typical features of heart failure such as myocardial stiffness and diastolic function impairment, the key characteristic of HFpEF is the normal left ventricular ejection fraction, which increases the difficulty of clinical diagnosis. QiShenYiQi Dripping Pills (QSYQ) is a standardized traditional Chinese medicine approved by the China Food and Drug Administration (CFDA), and many clinical studies have demonstrated the efficacy and safety of QSYQ in the treatment of heart failure with reduced ejection fraction, but the role of QSYQ in HFpEF has not been clarified. In this paper, high fat diet (HFD) and drinking water containing N-nitro-L-arginine methyl ester (L-NAME, 0.5 g·L-1, pH=7.4) were used in C57BL/6N male mice to construct the classical HFpEF model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220921002), and at the 8th week, the mice were dosed with ① empagliflozin, ② low-dose QSYQ (LQ), ③ high-dose QSYQ (HQ), ④ empagliflozin plus low-dose QSYQ (ELQ) for 4 weeks, the body weight of the mice was recorded during the experiment, echocardiography, blood pressure and glucose tolerance were detected and the exercise capacity of mice was evaluated, and pathological and biochemical experiments were used to detect cardiac fibrosis, liver fibrosis and serum biochemical indexes in mice, RNAseq assay was performed with mice heart tissues. The results showed that QSYQ as well as QSYQ+empagliflozin could significantly reduce the body weight, improve diastolic function and hypertension, improve glucose tolerance and enhance exercise ability of HFpEF mice. At the biochemical and molecular levels, QSYQ and QSYQ+empagliflozin can reduce the cross-sectional area of cardiomyocytes and reduce cardiac collagen contents, thereby alleviating myocardial hypertrophy and fibrotic phenotypes, and improve metabolic disorders. The RNAseq results suggest that the function of QSYQ in improving HFpEF may be related to calsequestrin 1. In conclusion, this study shows that QSYQ and QSYQ+empagliflozin can significantly improve HFpEF-related cardiac dysfunction and metabolic disorders, which provides a theoretical basis for the clinical treatment of HFpEF.