[Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy]

by Selleckchem | Aug 18 2023

Objective: To investigate the effect of Fuyu Decoction on ventricular remodeling and its association with AMPK/mTOR pathway-mediated autophagy in rats with heart failure.

Methods: Thirty male Wistar rat models of heart failure induced by ligation of the left anterior descending coronary artery were divided into model group, Fuyu Decoction treatment group, Fuyu Decoction treatment +AMPK agonist group (n=10), with another 10 rats receiving sham operation as the Sham group. After 8 weeks of drug intervention, the changes of ventricular function and ventricular remodeling indexs of the rats were assessed. TTC staining was used to detect the myocardial infarction area, and HE and Masson staining were used to observe the pathological changes in the myocardial tissue. Western blotting was performed to detect the protein expressions of p-AMPK, p-mTOR, LC3-II, Beclin1 and p62 in the myocardial tissue.

Results: Compared with the sham-operated rats, the rat models of heart failure showed significantly increased left ventricular end-diastolic volume (LVEDV), left ventricular endsystolic volume (LVESV), and left ventricular mass index (LVMI) (P < 0.01), reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and decreased spherical index (SI) were (P < 0.01). The rat models also showed increased myocardial infarction area, obvious myocardial pathologies and fibrosis, increased apoptosis rate of the cardiomyocytes, enhanced myocardial expressions of p-AMPK, LC3-II/LC3-I and Beclin1 (P < 0.01), and reduced expressions of p-mTOR and p62 (P < 0.01). Fuyu Decoction treatment significantly ameliorated these changes in the rat models (all P < 0.01), but its effects were obviously blocked by treatment with EX229.

Conclusion: Fuyu Decoction can improve ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR signaling-mediated autophagy in the cardiomyocytes.

Comments:

The objective of this study was to investigate the effect of Fuyu Decoction on ventricular remodeling in rats with heart failure and its association with the AMPK/mTOR pathway-mediated autophagy. The researchers conducted the study using male Wistar rat models of heart failure induced by ligation of the left anterior descending coronary artery. The rats were divided into different groups, including a model group, Fuyu Decoction treatment group, Fuyu Decoction treatment + AMPK agonist group, and a sham group.

After eight weeks of drug intervention, the researchers assessed the changes in ventricular function and ventricular remodeling indices in the rats. They used TTC staining to detect the myocardial infarction area and performed HE and Masson staining to observe the pathological changes in the myocardial tissue. Western blotting was conducted to measure the protein expressions of p-AMPK, p-mTOR, LC3-II, Beclin1, and p62 in the myocardial tissue.

The results of the study showed that compared to the sham-operated rats, the rat models of heart failure exhibited significantly increased left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular mass index (LVMI). Additionally, the heart failure models had reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and increased spherical index (SI). The rat models also displayed an increased myocardial infarction area, obvious myocardial pathologies and fibrosis, increased apoptosis rate of the cardiomyocytes, enhanced myocardial expressions of p-AMPK, LC3-II/LC3-I, and Beclin1, as well as reduced expressions of p-mTOR and p62.

However, treatment with Fuyu Decoction significantly ameliorated these changes in the rat models. The researchers observed improvements in ventricular remodeling, reduced myocardial infarction area, decreased pathologies and fibrosis in the myocardial tissue, decreased apoptosis rate, and normalized expressions of p-AMPK, LC3-II/LC3-I, Beclin1, p-mTOR, and p62.

Importantly, the effects of Fuyu Decoction on ventricular remodeling were found to be blocked by treatment with EX229, an AMPK agonist. This suggests that Fuyu Decoction improves ventricular remodeling by inhibiting AMPK/mTOR signaling-mediated autophagy in the cardiomyocytes.

In conclusion, Fuyu Decoction was shown to improve ventricular remodeling in rats with heart failure by inhibiting the AMPK/mTOR signaling-mediated autophagy in the cardiomyocytes. These findings provide valuable insights into the potential therapeutic effects of Fuyu Decoction in the management of heart failure.