Effect of trimetazidine on a rat model of bile duct ischemia-reperfusion injury and its mechanism
10.3969/j.issn.1001-5256.2022.11.021
- VernacularTitle:曲美他嗪对胆管缺血再灌注损伤大鼠模型的影响及其机制
- Author:
Jinrui ZHANG
1
,
2
;
Hao WU
1
,
2
;
Yi BAI
3
;
Yamin ZHANG
3
Author Information
1. The First Central Clinical College of Tianjin Medical University, Tianjin 300070, China
2. Ministry of Health Key Laboratory of Critical Illness and Emergency Medicine, Tianjin 300192, China
3. Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
- Publication Type:Original Articles_Biliary Diseases
- Keywords:
Reperfusion Injury;
Bile Ducts;
Trimetazidine;
Rats, Sprague-Dawley
- From:
Journal of Clinical Hepatology
2022;38(11):2546-2550
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of trimetazidine on ischemic bile duct injury in rats and related mechanism. Methods A total of 40 male Sprague-Dawley rats were randomly divided into sham-operation group (Sham group with 10 rats), bile duct ischemia-reperfusion injury group (BIRI group with 10 rats), 6-hour trimetazidine pretreatment group (TMZ-6h group with 10 rats), and 3-day trimetazidine pretreatment group (TMZ-3d group with 10 rats). The ischemia time was 30 minutes, and samples were collected after 24 hours of reperfusion. HE staining was used to observe bile duct injury, and the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and direct bilirubin (DBil) were measured, as well as the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in bile duct tissue; Western Blot was used to measure the levels of the signal molecules related to oxidative stress and apoptosis, such as nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (Bcl-2), and caspase-3. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Sidak t -test was used for further comparison between two groups. Results HE staining showed continuous interruption, necrosis, and exfoliation of bile duct epithelial cells in the BIRI group and no significant change in bile duct tissue in the TMZ-6h group, and in the TMZ-3d group, the bile duct epithelial cells had clear boundaries with a small amount of necrotic and exfoliated cells. Compared with the Sham group, the BIRI group had significant increases in the levels of ALT, ALP, DBil, and MDA (all P < 0.05); compared with the BIRI group, the TMZ-3d group had significant reductions in the levels of ALT, ALP, DBil, and MDA (all P < 0.05); there were no significant differences between the TMZ-6h group and the BIRI group (all P > 0.05). Compared with the Sham group, the BIRI group had a significant reduction in SOD activity ( P < 0.05), the TMZ-3d group had a significant increase compared with the BIRI group ( P < 0.05), and there was no significant difference between the TMZ-6h group and the BIRI group ( P > 0.05). Compared with the Sham group, the BIRI group had significant increases in the expression levels of Nrf2, HO-1, and caspase-3 (all P < 0.05) and a significant reduction in the expression level of Bcl-2 ( P < 0.05); compared with the BIRI group, the TMZ-3d group had significant increases in the expression levels of Nrf2, HO-1, and Bcl-2 ( P < 0.05) and a significant reduction in the expression level of caspase-3 ( P < 0.05); there were no significant differences in Nrf2, HO-1, Bcl-2, and caspase-3 between the TMZ-6h group and the BIRI group (all P > 0.05). Conclusion Trimetazidine can reduce bile duct ischemia-reperfusion injury in rats, possibly by inhibiting the level of oxidative stress in bile duct cells and reducing cell apoptosis.
