苏木酮A通过铁死亡对高脂饮食诱导的大鼠心肌脂毒性的 保护作用.

杨微微; 苏玉铭; 吴彬; 孙溶励; 李男

Objective To investigate the protective effect of sappanone A (SA) against high-fat diet-induced myocardial lipotoxicity through ferroptosis in rats. Methods Sixteen healthy male rats were equally divided into the normal diet (NCD) and model groups (n = 8) . Another 40 healthy male rats were equally divided into the high-fat diet (HFD), high-fat diet normal saline (HFD saline), high-fat diet low-dose SA (HFD 10 mg/kg SA), high-fat diet medium-dose SA (HFD 20 mg/kg SA), and high-fat diet high-dose SA (HFD 40 mg/kg SA) groups (n = 8) . Ultrasonography detected the changes in cardiac systolic function in the rats. Changes of myocardial hypertrophy, myocardial fibrosis, and myocardial cell apoptosis were evaluated by HE, Masson, Sirius red, and TUNEL staining. Differentially expressed genes in the myocardium of the HFD 20 mg/kg SA and HFD groups were analyzed by transcriptome sequencing. The SA signaling pathway was analyzed using the Kyoto Encyclopedia of Genes and Genomes. Results Compared with the NCD group, the model group had significantly increased left ventricular wall thickness, cross-sectional area of the myocardium, percentage of myocardial fibrosis, myocardial collagen deposition, and apoptosis, and significantly reduced short-axis shortening rate (all P < 0.05) . Compared with the HFD group, the SA treatment groups has significantly reduced left ventricular wall thickness, cross-sectional area of the myocardium, percentage of myocardial fibrosis, myocardial collagen deposition, and apoptosis, and significantly increased short-axis shortening rate (all P < 0.05) . Transcriptome sequencing revealed that ferroptosis was the most abundant pathway. Conclusion High-fat diet can induce myocardial lipotoxicity, and SA has a protective effect against myocardial lipotoxicity through ferroptosis.

HIGH-fat diet; CARDIAC hypertrophy; ENCYCLOPEDIAS & dictionaries; CELLULAR signal transduction; MYOCARDIUM

Journal of China Medical University, 2024, Vol 53, Issue 11, p1017

0258-4646

Academic Journal

10.12007/j.issn.0258‐4646.2024.11.011