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

Protective effect of sappanone A on high-fat diet-induced myocardial lipotoxicity through ferroptosis in rats

目的探讨苏木酮A(SA)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。方法将16只健康雄性大鼠分为正常饮食组(NCD组)和模型组,每组8只。将另外40只健康雄性大鼠分为高脂饮食组(HFD组)、高脂饮食+生理盐水组(HFD+saline组)、高脂饮食+低剂量SA组(HFD+10 mg/kg SA组)、高脂饮食+中剂量SA组(HFD+20 mg/kg SA组)和高脂饮食+高剂量SA组(HFD+40 mg/kg SA组),每组8只。采用超声心动图检测大鼠心脏收缩功能的改变,应用HE染色、Masson染色、天狼星红染色和TUNEL染色评估高脂饮食后心肌肥厚、心肌纤维化和心肌细胞凋亡的变化,比较不同组间大鼠上述指标的变化。通过心肌脂毒性大鼠模型的转录组测序分析HFD+20 mg/kg SA组和HFD组大鼠心肌中的差异基因,通过京都基因和基因组数据库分析SA作用的信号通路。结果与NCD组相比,模型组大鼠左心室室壁厚度以及心肌细胞横截面积、纤维化百分率、胶原纤维百分率和凋亡率显著增加,短轴缩短率显著降低(均P<0.05)。与HFD组相比,SA治疗组大鼠左心室室壁厚度以及心肌细胞横截面积、纤维化百分率、胶原纤维百分率和凋亡率呈现不同程度的降低,短轴缩短率呈现不同程度的升高(均P<0.05)。转录组测序发现,铁死亡信号通路为最主要富集的通路。结论高脂饮食可诱导心肌脂毒性,SA通过铁死亡对心肌脂毒性具有保护作用。

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.