Role of TFEB-autophagy pathway in rifampicin-induced liver injury and its mechanism
10.19405/j.cnki.issn1000-1492.2025.10.007
- VernacularTitle:TFEB⁃ 自噬途径在利福平所致肝损伤中的作用及其机制
- Author:
Hongmei Xu
1
;
Yulin Song
1
Author Information
1. Dept of Gastroenterology, The First Afiliated Hospital of Anhui Medical University, Hefei 230001
- Publication Type:Journal Article
- Keywords:
rifampicin;
liver injury;
TFEB;
autophagy;
cholestasis
- From:
Acta Universitatis Medicinalis Anhui
2025;60(10):1827-1832
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of transcription factor EB (TFEB) -autophagy pathway in rifampicininduced liver injury and its possible mechanism.
Methods:Forty 6-8-week-old C57/BL6 mice were randomly divided into five groups : control group , model group , TFEB low-dose agonist group , TFEB high-dose agonist group , and autophagy agonist group , with 8 mice in each group. Except for the control group , the other four groups were given rifampicin 200 mg/(kg ·d) by gavage daily. TFEB agonist was administered intraperitoneally at a low dose of 20 mg/kg and a high dose of 50 mg/kg for 7 days at 1 h after rifampicin administration. Autophagy agonist was administered by gavage at a dose of 10 mg/kg 6 h before rifampicin administration on day 1 . The experiment was completed 7 days after modeling. The degree of liver injury was evaluated by detecting liver function indexes and liver pathological changes. Western blot was used to detect the protein expression total TFEB , chelator 1( p62) , microtubule-associated protein light chain 3(LC3) , benzyl chloride 1(Beclin-1) , sodium taurocholate co-transporting polypeptide(NTCP) and bile salt export pump(BSEP) levels in liver nucleus/liver tissue were quantified.
Results:Compared with the control group , the serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase (AST) , total bilirubin ( TBIL) , direct bilirubin ( DBIL) , and total bile acid ( TBA) in the model group increased (P < 0. 05) , and obvious pathological changes were observed in the liver. Compared with the model group , the high dose and low dose of TFEB agonist and autophagy agonist groups had reductions in the above indicators (P < 0. 05) . Compared with the low-dose TFEB agonist group , the high-dose TFEB agonist group had reductions in the above indicators (P < 0. 05) . The proportion of TFEB in the nucleus was ( 1. 0 ± 0. 10) in the control group , (0. 6 ± 0. 05) in the model group , (0. 8 ± 0. 08) in the low-dose agonist group , and (0. 9 ± 0. 07) in the high-dose agonist group (P < 0. 05) . Autophagy agonist group (0. 7 ± 0. 06) (P < 0. 05) . Compared with the control group , the levels of NTCP and BSEP in the liver of the model group decreased (P < 0. 05) , and the expression of NTCP and BSEP in the TFEB low-dose and high-dose agonist groups were restored , and the expression of NTCP and BSEP in the autophagy agonist group also increased (P < 0. 05) . Compared with the control group , the protein expression levels of TFEB , LC3- Ⅱ/LC3- Ⅰand Beclin-1 in the liver tissue of the model group significantly decreased (P < 0. 05) , while the protein expression level of p62 significantly increased ( P < 0. 05) . Compared with the model group , the protein expression levels of TFEB , LC3- Ⅱ/LC3- Ⅰand Beclin-1 in the liver tissue of the TFEB agonist high-dose group , low-dose group and autophagy agonist group increased (P < 0. 05) , while the protein expression level of p62 decreased (P < 0. 05) .
Conclusion:TFEB can improve rifampicin-induced liver injury by activating autophagy pathway , and the main mechanism may be related to the up-regulation of NTCP and BSEP expression.
- Full text:2026030721261221758TFEB-自噬途径在利福平所致肝损伤中的作用及其机制_徐红梅.pdf
