Salvianolic acid B mediates Elovl6/Echs1/Acot1 pathway to regulate fatty acid metabolism and attenuates OGD/R injury in H9c2 cells
- VernacularTitle:丹酚酸B介导Elovl6/Echs1/Acot1通路调节脂肪酸代谢减轻H9c2细胞OGD/R损伤
- Author:
Ce CAO
1
;
Jian-shu SONG
1
;
Li-li YANG
1
;
Hao-ran LI
1
;
Zi-xin LIU
1
;
Lei LI
1
;
Jian-hua FU
1
;
Jian-xun LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: salvianolic acid B; transcriptome high-throughput sequencing; H9c2 cardiomyocytes; OGD/R; ischemia-reperfusion injury; fatty acid metabolism
- From: Chinese Pharmacological Bulletin 2025;41(3):482-490
- CountryChina
- Language:Chinese
- Abstract: Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.
