Critical Care Medicine
Role of CD73 in endogenous protective mechanism of hepatic ischemia-reperfusion injury in mice and the relationship with TGF-β1/Smad3 signaling pathway
Hu Zhanfei, Zhang Yanjun, Guo Hao, Wang Li, Yu Wenli, Du Hongyin
Published 2022-05-20
Cite as Chin J Anesthesiol, 2022, 42(5): 595-599. DOI: 10.3760/cma.j.cn131073.20220106.00519
Abstract
ObjectiveTo evaluate the role of ecto-5′-nucleotidase (CD73) in endogenous protective mechanism of hepatic ischemia-reperfusion (I/R) injury in mice and the relationship with transforming growth factor beta1 (TGF-β1)/Smad3 signaling pathway.
MethodsTwenty-four SPF healthy male C57BL/6 mice, aged 8-10 weeks, weighing 20-23 g, were divided into 3 groups (n=8 each) by the random number table method: sham operation group (S group), hepatic I/R group (IR group) and hepatic I/R plus CD73 specific inhibitor group (APCP group). The hepatic hilum was only exposed but not occluded in group S. The hepatic portal was occluded for 30 min followed by reperfusion to develop the model of hepatic I/R in anesthetized animals in group IR.CD73-specific inhibitor APCP 40 mg/kg was intraperitoneally injected, and 10 min later hepatic I/R was performed.Orbital venous blood samples were collected at 6 h of reperfusion for determination of serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations.Then the mice were sacrificed, and liver tissues were obtained for determination of the expression of CD73, TGF-β1 and phosphorylated Smad3 (p-Smad3) (by Western blot), contents of interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), and content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) (with a visible spectrophotometer) and for microscopic examination of the pathological changes of liver tissues (with a light microscope).
ResultsCompared with group S, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β1 and p-Smad3 was up-regulated in IR and APCP groups (P<0.05). Compared with group IR, the concentrations of AST and ALT in serum and contents of IL-1β, TNF-α and MDA in liver tissues were significantly increased, the activity of SOD was decreased, and the expression of CD73, TGF-β1 and p-Smad3 in liver tissues was down-regulated in group APCP (P<0.05). The pathological changes of liver tissues were accentuated in group APCP as compared with group IR.
ConclusionsCD73 is involved in the process of endogenous protective mechanism of hepatic I/R injury in mice, which may be related to the regulation of TGF-β1/Smad3 signaling pathway.
Key words:
5′-Nucleotidase; Liver; Reperfusion injury; Transforming growth factor beta; Smad3 protein
Contributor Information
Hu Zhanfei
First Central Clinic College, Tianjin Medical University, Tianjin 300192, China
Zhang Yanjun
First Central Clinic College, Tianjin Medical University, Tianjin 300192, China
Guo Hao
First Central Clinic College, Tianjin Medical University, Tianjin 300192, China
Wang Li
First Central Clinic College, Tianjin Medical University, Tianjin 300192, China
Yu Wenli
Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China
Du Hongyin
Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China
