Protective effects of HDAC inhibitors combined with bone marrow mesenchymal stem cells on acute hepatocyte injury
10.13699/j.cnki.1001-6821.2024.24.015
- VernacularTitle:HDAC抑制药联合骨髓间充质干细胞对急性肝细胞损伤的保护作用
- Author:
Li-xia CHEN
1
;
Jian-hui LIN
;
Min CHEN
;
Wen-guo XIE
Author Information
1. 福建医科大学孟超肝胆医院肝内科,福建 福州 350000;福建医科大学孟超肝胆医院人工肝中心,福建 福州 350000
- Publication Type:Journal Article
- Keywords:
histone deacetylase inhibitor;
acute liver failure;
bone marrow mesenchymal stem cells;
mitochondrial autophagy;
apoptosis
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(24):3595-3600
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of histone deacetylase(HDAC)inhibitor CAY10683 combined with bone marrow mesenchymal stem cells(MSCs)on acute liver failure(ALF).Methods L-02 cells were cultured in vitro.The cells were randomly divided into normal group(normal cultured cells),model group[40 mmol·L-1 D-galactosamine(D-GalN)+1 μg·mL-1 lipopolysaccharide(LPS)intervention],MSCs group(D-GalN/LPS induced and co-cultured with MSCs),CAY10683 group(D-GalN/LPS+5 μmol·L-1 CAY10683),combined group(D-GalN/LPS+5 μmol·L-1CAY10683 treatment and co-cultured with MSCs).The cell viability was detected by cell counting kit-8(CCK-8)assay.The apoptosis rate was detected by flow cytometry.The activity of glutamic-oxaloacetic transaminase(GOT)was detected by kit.The cell membrane potential was detected by JC-1 assay.The protein expression was detected by Western blotting.The level of reactive oxygen species(ROS)was detected by kit method.Results The cell survival rates of normal group,model group,MSCs group,CAY10683 group and combined group were(100.00±4.07)％,(60.47±4.54)％,(72.11±4.63)％,(75.46±3.29)％and(85.45±9.08)％,respectively;the apoptosis rates were(4.30±0.42)％,(22.96±3.06)％,(17.69±1.18)％,(16.63±0.15)％and(10.24±0.08)％,respectively;the GOT activities were(5.83±0.52),(10.90±1.16),(9.10±0.69),(8.89±0.91)and(7.04±0.64)U·mL-1,respectively;the red/green fluorescence ratios of mitochondrial membrane potential were 1.00±0.06,0.51±0.05,0.73±0.04,0.71±0.08 and 0.87±0.11,respectively;the protein levels of autophagy-related microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ were 1.94±0.27,0.52±0.08,0.89±0.14,0.84±0.13 and 1.89±0.28,respectively;the ROS levels were(100.00±6.08)％,(179.73±11.79)％,(140.80±14.58)％,(135.19±10.04)％and(121.61±9.10)％,respectively.The above indicators of the model group were compared with the control group,the above indicators of the MSCs group,the CAY10683 group,and the combined group were compared with the model group,and the above indicators of the combined group were compared with the MSCs group and the CAY10683 group,the differences were statistically significant(all P＜0.05).Conclusion CAY10683 combined with MSCs can induce mitochondrial autophagy,improve mitochondrial damage and inhibit L-02 cell apoptosis induced by D-GalN/LPS.
