Protective effect of serine methyltransferase against hepatic ischemia-reperfusion injury in mice.
10.12122/j.issn.1673-4254.2020.04.09
- Author:
Yu JIANG
1
;
Ankang WANG
1
;
He BAI
2
;
Mingxin YE
1
Author Information
1. Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
2. Department of General Surgery, First Affiliated Hospital of Xi'an Medical College, Xi'an 710000, China.
- Publication Type:Journal Article
- Keywords:
JNK;
hepatic ischemia-reperfusion;
nuclear factor-κB;
serine hydroxymethyl transferase
- MeSH:
Animals;
Apoptosis;
Liver;
Methyltransferases;
Mice;
Mice, Inbred C57BL;
NF-kappa B;
Reperfusion Injury;
Serine
- From:
Journal of Southern Medical University
2020;40(4):506-512
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the protective effect of serine hydroxymethyl transferase 2 (SHMT2) against hepatic ischemia-reperfusion injury in mice.
METHODS:Sixty C57BL/6 mice were divided equally into sham-operated group, saline adeno-associated virus group (AVV-GFP), and adeno-associated virus silencing group (AAV-SHMT2). The adeno-associated virus and normal saline were injected into the tail vein of the mice 2 weeks before establishment of a 70% ischemia-reperfusion model in the liver. qPCR, Western blotting, immunofluorescence and immunohistochemistry were used to detect the changes of AST/ALT concentration, SHMT2, JNK, NF-κB, caspase-3 and downstream inflammatory factors in the mice, and HE staining was used to observe the pathological damage of the liver tissue in each group; the cell apoptosis in the liver was detected using TUNEL assay.
RESULTS:The expression of SHMT2 increased with time after hepatic ischemia-reperfusion and reached the highest level at 24 h (the relative expression was 1.5, < 0.05). At 24 h after hepatic ischemia-reperfusion, the levels of AST/ALT in AAV-SHMT2 group (588/416 U/L) were significantly higher than those in the control group (416/345 U/L) and the empty vector group (387/321 U/L) ( < 0.05). Compared with those in the control group and the empty vector group, the level of SHMT2 was significantly decreased in AAV-SHMT2 group (with a relative expression of 0.24, < 0.05), the levels of p-JNK and p-p65 were significantly increased (relative expression of 0.80 and 0.97, respectively, < 0.05), and the levels TNF-α and IL-1β were consistently elevated (relative expression levels of 1.6 and 1.2, respectively, < 0.05). No significant differences were found in these parameters between the empty vector group and the control group (>0.05).
CONCLUSIONS:SHMT2 may alleviate liver cell apoptosis in mice with hepatic ischemia-reperfusion injury by inhibiting the activation of JNK pathway and excessive activation of NF-κB pathway to reduce hepatic damage.
