淫羊藿苷通过上调SLC7A11/GPX4轴减轻铁死亡改善心力衰竭

Icariin ameliorates heart failure by attenuating ferroptosis through the upregulation of the SLC7A11/GPX4 axis

目的 基于脂质过氧化研究淫羊藿苷抗异丙肾上腺素所致小鼠心力衰竭的作用机制。方法 将C57BL/6小鼠随机分为空白组、异丙肾上腺素模型组(ISO,15 mg/kg)、氯沙坦阳性药组(Los, 9 mg/kg),以及淫羊藿苷低剂量组(ICA-L组,15 mg/kg)、淫羊藿苷高剂量组(ICA-H组,60 mg/kg)。采用小动物超声检测仪检测小鼠心功能(EF%、FS%)的变化,计算小鼠心脏指数。采用HE染色观察小鼠左心室组织病理变化,采用布鲁士蓝染色观察小鼠左心室组织铁离子的积累。采用Western blot检测小鼠左心室组织中铁死亡相关蛋白SLC7A11、GPX4、4-HNE、ACSL4、LPCAT3、TFR1、DMT1的表达。结果 ICA和Los可以改善ISO引起的小鼠左心室射血分数和短轴缩短率的降低,减轻ISO所致的左心室组织病理损伤以及铁离子过度积累,抑制ISO所致左心室组织中SLC7A11、GPX4蛋白的下调,4-HNE、ACSL4、LPCAT3、TFR1、DMT1蛋白的上调(P<0.05)。结论 ICA可能通过上调SLC7A11/GPX4轴抗脂质过氧化,减轻铁死亡,改善ISO所诱导的小鼠心力衰竭。

Objective To study the mechanism of Icariin anti-isoproterenol induced heart failure in mice based on lipid peroxidation inhibition.Methods C57BL/6 mices were randomly divided into a control group,an isoproterenol model group(ISO,15 mg/kg),a losartan positive drug group(Los,9 mg/kg),a low-dose Icariin group(ICA-L group,15 mg/kg),and a high-dose Icariin group(ICA-H group,60 mg/kg).Small animal ultrasound detector was used to detect changes in mouse heart function;the mouse heart index was calculated;HE staining was used to observe the pathological changes in the left ventricular tissue of mice;Bruce blue was used to stain the accumulation of iron ions in the left ventricular tissue of mice;Western blot was used to detect the expression of iron death related proteins(SLC7A11,GPX4,4-HNE,ACSL4,LPCAT3,TFR1,DMT1)in mouse left ventricular tissue.Results ICA and Los improved the ISO-decreased left ventricular ejection fraction(EF%)and left ventricular fractional shortening(FS%),alleviated the pathological damage and excessive accumulation of iron ions in the left ventricular tissue caused by ISO,inhibited the downregulation of SLC7A11 and GPX4 proteins in the left ventricular tissue caused by ISO,and upregulated 4-HNE,ACSL4,LPCAT3,TFR1 and DMT1 proteins(P<0.05).Conclusion ICA upregulates the SLC7A11/GPX4 axis against lipid peroxidation,attenuating ferroptosis improves heart failure in mice.