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《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:

2023年03期

页码:

165-169

栏目:

基础研究

出版日期:

2023-05-30

文章信息/Info

Title:

Effect of ferroptosis on cardiac dysfunction in type 1 diabetic cardiomyopathy in mice?

作者:

卢清; 和凤; 王文秋; 王焱林; 柯剑娟

430071 武汉大学中南医院麻醉科

Author(s):

LU Qing; HE Feng; WANG Wenqiu; WANG Yanlin; KE Jianjuan

Department of Anesthesiology,Zhongnan Hospital of Wuhan University, Wuhan 430071, China

关键词:

铁死亡; 糖尿病心肌病; 心功能障碍

Keywords:

Ferroptosis;  Diabetic cardiomyopathy;  Cardiac dysfunction

分类号:

-

DOI:

10.3969/j.issn.1673-6583.2023.03.010

文献标识码:

-

摘要:

目的：探讨铁死亡在1型糖尿病心肌病（DCM）小鼠心功能障碍中的作用。?方法：选取清洁级健康成年雄性C57BL/6小鼠36只，随机分为对照组、DCM组和铁死亡抑制剂Ferrostatin-1组（Fer-1组），每组12只。DCM组和Fer-1组采用连续5d腹腔注射新鲜制备的链脲佐菌素（STZ）40mg/(kg·d)后继续饲养12周的方法建立1型糖尿病DCM小鼠模型。自建模起第2周末，Fer-1组小鼠连续10周腹腔注射铁死亡抑制剂Fer-12.5μmol/(kg·d)，对照组和DCM组小鼠给予等量二甲基亚砜（DMSO）。第12周末行超声心动图检查，采用苏木精-伊红（HE）染色观察小鼠心肌组织病理形态学变化，透射电镜观察小鼠心肌组织超微结构，Westernbolt法检测小鼠心肌组织中铁死亡相关蛋白表达情况。结果：与对照组相比，DCM组小鼠出现明显心功能障碍；HE染色显示心肌细胞肥大且排列紊乱，炎性细胞浸润；透射电镜显示心肌细胞线粒体形态学改变，包括线粒体变小，膜密度增高，线粒体皱缩，线粒体嵴减少或消失；Westernblot结果显示心肌组织谷胱甘肽还原酶4（GPX4）的蛋白表达水平均显著降低，酯酰辅酶A合成酶长链家族成员4（ACSL4）的蛋白表达水平显著升高（P均＜0.05）。与DCM组比，Fer-1组小鼠心功能障碍减轻，心肌组织GPX4的蛋白表达水平均显著升高，ACSL4的蛋白表达水平显著降低（P均＜0.05），心肌组织病理改变明显减轻。?结论：铁死亡参与了1型糖尿病DCM小鼠心功能障碍的发病过程。

Abstract:

Objective: To investigate the effect of ferroptosis on cardiac dysfunction in type 1 diabetic cardiomyopathy (DCM) in mice.? Methods: A total of 36 healthy adult male C57BL/6 mice were randomly divided into control group, DCM group, and ferroptosis inhibitor ferrostatin-1 group (Fer-1 group), with 12 mice in each group. DCMmodel was built by intraperitoneal injection of freshly prepared streptozotocin (STZ) 40 mg·kg-1·d-1 for 5 consecutive days, then mice were fed for additional 12 weeks. Fer-1 (2.5 μmol·kg-1·d-1) was given intraperitoneally after the second week in Fer-1 group, while equal volume of dimethyl sulfoxide (DMSO) was administered in control and DCM groups. At 12 weeks, echocardiography was performed to assess cardiac function, then all mice were sacrificed. Myocardial pathological and ultrastructural changes were examined by hematoxylin-eosin (HE) staining and transmission electron microscope (TEM), respectively. Expression of ferroptosis protein was assessed by western bolt.? Results: Compared with control group, distinct cardiac dysfunction was detected in DCM group. HE staining showed cardiomyocyte hypertrophy, irregular arrangement and inflammatory cell infiltration, and TEM revealed certain abnormal morphological features of mitochondria, including shrunken mitochondria with increased membrane density and mitochondrial ridge reduction or even disappearance in DCM group. Western blot indicated that for DCM group, the expression levels of glutathione reductase 4 (GPX4) were decreased, whereas the expression levels of esteryl CoA synthetase long chain member 4 (ACSL4) were increased in the myocardial tissue (all P＜0.05). Treatment with Fer-1 resulted in a remarkable improvement in cardiac function and an increase in expression levels of GPX4 and a decrease in expression levels of ACSL4 in the myocardial tissue (all P＜0.05). The pathological changes in the myocardial tissue were alleviated as well.? Conclusion: Ferroptosis is involved in the process of cardiac dysfunction in type 1 diabetic cardiomyopathy in mice.

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备注/Memo

备注/Memo:

基金项目：国家自然科学基金（81471858, 81871553）

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更新日期/Last Update: 2023-05-30