Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice  

作　　者：Ori Rotstein 

机构地区：[1]Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2004年第2期250-253,共4页国际肝胆胰疾病杂志（英文版）

摘　　要：BACKGROUND: Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepa- tic ischemia/reperfusion (I/R) injury in mice. METHODS: TLR4-deficient mice ( C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by oc- clusion of inflow to the median and left lobes for 45 mi- nutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-α). TNF-α mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively. RESULTS: AST levels were significantly decreased in TLR4- deficient mice compared with WT mice at both time points (WT: 1215.5 ±174. 03, 2958. 17 ± 186. 81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83±106.09, 1145.17± 132.43 IU/L at 1 and 3 hours, mean ± SD, 6 mice/group, (=-6.65 and -5.57, P <0.001). Consistent with the role of TNF-α in hepatic I/R, serum TNF-α was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39±43.3 vs 249.12 ± 51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 defi- cient mice at 3 hours after reperfusion was significantly low- er than that in WT mice (0.059±0.004 vs 0.173±0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-α mRNA expression at 1 hour after reperfu- sion compared with WT mice (80.3±28.8 vs 189.4±24.6, t=-3.25, P<0.05). CONCLUSIONS: Compared with WT mice, TLR4-defi- cient mice appear to have a mild I/R injury. Regulation of TNF-a at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of he-patic I/R injury in mice.BACKGROUND: Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepa- tic ischemia/reperfusion (I/R) injury in mice. METHODS: TLR4-deficient mice ( C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by oc- clusion of inflow to the median and left lobes for 45 mi- nutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-α). TNF-α mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively. RESULTS: AST levels were significantly decreased in TLR4- deficient mice compared with WT mice at both time points (WT: 1215.5 ±174. 03, 2958. 17 ± 186. 81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83±106.09, 1145.17± 132.43 IU/L at 1 and 3 hours, mean ± SD, 6 mice/group, (=-6.65 and -5.57, P <0.001). Consistent with the role of TNF-α in hepatic I/R, serum TNF-α was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39±43.3 vs 249.12 ± 51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 defi- cient mice at 3 hours after reperfusion was significantly low- er than that in WT mice (0.059±0.004 vs 0.173±0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-α mRNA expression at 1 hour after reperfu- sion compared with WT mice (80.3±28.8 vs 189.4±24.6, t=-3.25, P<0.05). CONCLUSIONS: Compared with WT mice, TLR4-defi- cient mice appear to have a mild I/R injury. Regulation of TNF-a at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of he-patic I/R injury in mice.

关 键 词：LIVER ISCHEMIA/REPERFUSION INJURY toll-like receptor ENDOTOXIN 

分 类 号：R575[医药卫生—消化系统]