The relationship between activation of TLR4 and partial hepatic ischemia/reperfusion injury in mice

Objective To explore the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. Methods BALB/c mice were used in a model of partial hepatic I/R injury, the distribution of TLR4 in liver was observed with immunohistochemical stains. The level of plasma ALT and endotoxin in portal vein were measured. TLR4-deficient mice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury, the hepatic function and serum TNF-α were observed. Results 1. After one hour ischemia the expression of TLR4 protein increased at 1 st, 3 rd h of reperfusion. especially in Kupffer cells, followed by Granno-monocyte and liver sinus epithelial cell; 2. No endotoxemia developed; 3. At 3 rd h of reperfusion, serum TNF-α was significantly higher than sham group [Hej: (152±43)pg/ml vs. (18±10)pg/ml, n=6, t=5.26, P0.01; Heouj: (249±52)pg/ml vs. (25±13)pg/ml, n=6, t=7.24, P0.01]; 4. At 1 st h and 3 rd h reperfusion, serum ALT in Hej mice was lower than Heouj mice [1 sth: (662±106)pg/ml vs. (1?216±174)pg/ml, n=6,t=4.21,P0.01; 3 sth: (1?145±132)pg/ml vs. (2?958±187)pg/ml, n=6, t=13.72, P0.01] serum TNF-α was lower than Heouj mice [(152±43)pg/ml vs. (249±52)pg/ml, n=6, t=3.94, P0.01] at 3 h reperfusion. Conclusion TLR4 activated in the process of partial hepatic I/R injury together with TNF-α plays a role in I/R injury.