ATRA alleviates lipopolysaccharide －induced acute myocardial injury in mice by inhibiting Ferroptosis
10.19405/j.cnki.issn1000-1492.2023.03.005
- Author:
Zhangyong Dan
1
;
Chuanlin Shu
1
;
Xiaorui Shi
1
;
Qing Zhou
1
;
Yuan Wang
1
;
Mengfei Ren
2
;
Yi3 Wang
3
;
Huaqing Zhu
1
Author Information
1. Dept of Biochemistry and Laboratory of Molecular Biology of Anhui Medical University，Hefei 230032
2. Dept of College of Life Sciences，Anhui Medical University，Hefei 230032
3. Dept of Bioengineering，College of Life Sciences，Anhui Medical University，Hefei 230032
- Publication Type:Journal Article
- Keywords:
all-trans retinoic acid;
ferroptosis;
NRF2;
lipopolysaccharide
- From:
Acta Universitatis Medicinalis Anhui
2023;58(3):373-378
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice．
Methods :Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) .
Results:Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．
Conclusion:ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.
- Full text:2024071611273488539ATRA通过抑制铁死亡缓解...多糖诱导的小鼠急性心肌损伤_但章勇.pdf
