Study On Tle1 Attenuating Hepatic Ischemia/Reperfusion Injury By Inhibiting NOD2

Objective: To explore the role of Tle1 in hepatic ischemia/reperfusion injury and the specific molecular mechanism.Methods: Mouse models of liver I/R and cell models of H/R were established,and the expression of Tle1 and NOD2 was regulated by siRNA.qRT-PCR was used to detect mRNA levels of Tle1,NOD2 and TNF-?;Western blot was used to detect protein levels of Tle1,NOD2,p-p65,p65,p-I?B?,I?B? and IL-1?;liver function test kits were used to detect serum AST and ALT levels;ELISA kits were used to detect IL-1?,IL-6 and TNF-? levels in the serum and cell supernatants;H&E staining was used to examine morphological changes such as congestion,vacuoles and necrosis of liver tissues.Results: After I/R treatment,the expression of Tle1 in the liver tissues was significantly decreased,and the expression of NOD2 and TNF-? was prominently increased.Similarly,after H/R treatment,the expression of Tle1 in the cells was notably decreased,and the expression of NOD2 and TNF-? was remarkably increased.In the mouse models of liver I/R,compared with the Tle1 non-knockdown groups,liver tissues in the Tle1 knockdown groups showed more severe congestion,vacuoles,and necrosis,and serum levels of AST,ALT,IL-1?,IL-6,and TNF-? were drastically enhanced.In the cell models of H/R,the protein expression of NOD2,p-p65,p-I?B?,and IL-1? in the Tle1 knockdown groups was up-regulated when compared to the Tle1 non-knockdown groups.At the same time,the levels of IL-1?,IL-6,and TNF-? in cell supernatant were increased.However,the protein expression of Tle1 in the NOD2 knockdown groups and the NOD2 non-knockdown groups was almost the same.Conclusion: Tle1 can reduce liver damage caused by I/R,and the specific mechanism may be related to the inhibition of NOD2/NF-?B signaling.