The Effect Of SOCS-1 And SOCS-3 Protein Expression On Galn/LPS Induced-acute Liver Damage

Aim: With using mice endotoxin tolerance models,discusses the effect of SOCS-1 and SOCS-3 protein expression on acute liver damage caused by Galn/LPS。Methods: Mouse randomly divided into endotoxin control group (Control), liver injury group (Galn/LPS) and tolerance group (ETT) , control group accept intraperitoneal injection of 0.9%NaCl 0.2ml, ETT group intraperitoneal inject low-dose of LPS 0.5mg/kg 3 times,each time intervals for 24 hours,On the fourth day intraperitoneal inject D-GalN 20mg/kg,LPS4μg per mice,Galn/LPS group just accept the same doses of D-Galn/LPS injections on the 4th day.Take plasma and liver of ETT and LPS group in 1,1.5,3,6hours after D - Galn/LPS injection,Then take plasma and the liver of the control group. Test 1.5 hours liver tissue tumor necrosis factorα(TNF-α)with ELISA determination,6 hours liver tissue interleukin 10 (IL - 10) with the same method, 6 hours plasma alanine aminotransferase (ALT) level with King 's unit determination. HE staining of 6 hours liver tissue, Western blot detect 1,3, 6 hours SOCS– 1,SOCS-3,IRAK-4 and 6h P-STAT3 protein expression in the liver tissue.Results:LPS pretreatment can significantly reduce acute liver damage caused by Galn/LPS . Plasma ALT activity decline significantly(p<0.05), while IL - 10 content increased significantly(p<0.05). Liver homogenate TNFαmeasurement indicates that the ETT group TNF-αwas obviously higher than that of the Galn/LPS group and control group(p<0.05).The SOCS-1 and SOCS-3 protein expression of Galn/LPS group were all closed to their highest level at 1h after Galn/LPS intraperitoneal injection,then decreased gradually at 3h and get to their lowest level at 6h.The tendency of SOCS-1 and SOCS-3 protein expression of ETT group were similar to Galn/LPS group's,but they were all higher than Galn/LPS group's at each time point(P <0.05).The IRAK-4 protein expression increased significantly at 1h, and get to it's highest level at 6h(P <0.05).The intraperitoneal injection of Galn/LPS could significantly induce the phosphorylation of STAT-3(P <0.05),but pretreatment of LPS could inhibit the level of STAT-3 phosphorylation significantly(P <0.05).Conclusion: ETT could induce SOCS-1,SOCS-3,IRAK-4 proteins expression,inhibit the STAT signal transduction, reduce plasma TNF-αlevel,increase plasma IL-10 level and decrease liver damage caused by Galn/LPS.