The effect and mechanism of tacrolimus pretreatment on cold ischemia reperfusion injury of transplanted liver in rats
10.3760/cma.j.cn113884-20200107-00009
- VernacularTitle:他克莫司预处理对大鼠自体原位肝移植冷缺血再灌注损伤的影响和机制
- Author:
Lijie ZHANG
1
;
Feng CHEN
;
Xiaodong DU
;
Xiaohua JU
;
Qing WANG
;
Xiaohua ZHAO
Author Information
1. 潍坊医学院人体解剖学实验室，潍坊 261053
- From:
Chinese Journal of Hepatobiliary Surgery
2020;26(7):547-550
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the roles of tacrolimus pretreatment on hepatic ischemia reperfusion injury (IRI) and its possible mechanism in a rat autologous orthotopic liver transplantation (AOLT) model.Methods:For 24 specific pathogen free 8-10 week male Sprague Dawley rats (220-250g) were randomly and equally divided into three groups. The abdomen of sham-operated group was only opened and closed; the treatment with tacrolimus was administered via dorsal penile vein before the experiment in tacrolimus-pretreated group; the AOLT group and tacrolimus-pretreated group were set to construct the AOLT IRI rat models. The levels of ALT, AST, tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in serum were tested after the reperfusion. The change of liver structure was evaluated by H&E staining. The quantitative real-time PCR (RT-qPCR) and Western blot assay were used to test the mRNA and protein level of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HO-1).Results:The levels of serum ALT (1 332.0±52.8) U/L and AST (2 472.0±257.8) U/L in the AOLT group were higher than the levels in the sham-operated group (65.0±17.4)U/L, (222.3±45.2) U/L and tacrolimus-pretreated group (789.9±54.0) U/L, (533.4±31.6) U/L. The differences were significant ( P<0.05). And in the tacrolimus-pretreated group there were less lesions in the liver than in the AOLT group. The serum level of TNF-α and IL-1β of the AOLT group were increased than the sham-operated group and tacrolimus-pretreated group, and the differences were significant ( P<0.05). Compared with the AOLT group, the expressions of HIF-1α and HO-1 were increased significantly after the tacrolimus pretreatment ( P<0.05). Conclusion:Tacrolimus pretreatment could reduce rats hepatic cold IRI by inducing the expressions of HIF-1α and HO-1, and inhibiting the production of inflammatory cytokines.
