Psoralen attenuates skeletal muscle atrophy in mice with heart failure after myocardial infarction by regulating NLRP3/Caspase-1/GSDMD pathway
Abstract
This study aimed to explore the therapeutic effects of psoralen(PSO) on skeletal muscle atrophy in chronic heart failure(CHF) and its underlying mechanisms. Male mice were randomly assigned to control, CHF, high-dose PSO, low-dose PSO, and empagliflozin(empa) groups. A CHF model was established by ligating the left anterior descending coronary artery, which was followed by 8 weeks of treatment starting 2 weeks post-surgery. In vitro, C2C12 myoblasts were cultured and exposed to angiotensin Ⅱ(Ang Ⅱ) to induce skeletal muscle injury, and divided into control, Ang Ⅱ, low-/medium-/high-dose PSO, and pyroptosis induction(nigericin) groups. General conditions, body weight, and skeletal muscle mass were recorded. The left ventricular ejection fraction(LVEF) was assessed by echocardiography. Skeletal muscle function was evaluated using grip strength and rotarod tests. Histopathological changes were examined by hematoxylin-eosin(HE) staining. Levels of interleukin IL-1β and tumor necrosis factor-α(TNF-α) in skeletal muscle tissue were measured. Transcriptomic profiling was performed to observe gene changes of mice and thereby predict relevant biological processes. Immunohistochemistry was used to evaluate NOD-like receptor family pyrin domain containing 3(NLRP3), cleaved-Caspase-1(c-Caspase-1), and N-terminal fragment of gasdermin D(GSDMD-N) expression. Western blot quantified NLRP3, GSDMD, GSDMD-N, Caspase-1, c-Caspase-1, and IL-1β protein levels. Immunofluorescence was employed to…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.