Overexpression of TRIM27 alleviates severe acute pancreatitis in mice by inhibiting NFκB/MAPK signaling pathway / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the protective effect of overexpressed tripartite motif containing (TRIM27) on severe acute pancreatitis (SAP) in mice and its possible mechanism.Methods:Twenty-four mice were randomly divided into the sham operation + control virus group (AAV-GFP group), sham operation + overexpression of TRIM27 group (AAV-TRIM27 group), SAP + control virus group (SAP+AAV-GFP group), SAP + overexpression of TRIM27 group (SAP + AAV-TRIM27 group), with 6 mice in each group. SAP model of mice was established by intraperitoneal injection of L-arginine (4 mg/kg). The sham operation group was injected with equal volume of normal saline, and the virus group was injected with control or TRIM27 overexpression adeno-associated virus (2×10 11 μg/ per mice). The serum and pancreatic tissue samples were collected 72 h after modeling. The levels of serum amylase, lipase, tumor necrosis factor α (TNF-α), interleukin-1b (IL-1b), IL-6, macrophage chemoattractant protein-1 (MCP-1) and the expression of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) in pancreatic tissue were detected by enzyme-linked immunosorbent assay. Hematoxylin eosin staining was used to observe the pathological damage of pancreatic tissue. The expressions of myeloperoxidase (MPO) and Ly6g positive inflammatory cells in mouse pancreas were observed by immunohistochemistry. The expression of p-p65, p65, p-ASK1, ASK1, p-JNK, JNK, p-p38 and p38 in pancreatic tissue were detected by Western blot. Results:The expression of TRIM27 in pancreatic of mice was significantly down regulated after SAP ( P<0.05); after overexpression of TRIM27 by adeno-associated virus, the expression of TRIM27 in mouse pancreas was significantly up-regulated ( P<0.05). There was no significant difference in the indexes of mice between the AAV-GFP group and AAV-TRIM27 group ( P>0.05). Compared with the SAP + AAV-GFP group, the levels of serum amylase, lipase, TNF-α, IL-1b, IL-6 and MCP-1 in mice of the SAP + AAV-TRIM27 group were significantly decreased, MDA in pancreatic tissue was decreased, SOD and GSH were increased, MPO and Ly6g inflammatory cells were significantly decreased, and p-p65, p-ASK1, p-JNK, and p-p38 protein expression were down regulated. Conclusions:Overexpression of TRIM27 alleviates SAP in mice by inhibiting inflammatory response and oxidative stress, and its mechanism may be through inhibiting NFκB/MAPK signaling pathway.