Significance of rosiglitazone inhibiting TLR4 expression in partial hepatic ischemia/reperfusion of mice.
The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptor gamma (PPARgamma) inhibiting the TLR4 expression in ischemic lobes in partial hepatic ischemia/reperfusion injury (IRI) in BALB/C mice and the action of rosiglitazone inhibiting the TLR4 receptor-mediated inherent immune response were investigated. The model of the mouse partial hepatic ischemia/reperfusion injury was established. All the animals were randomly divided into 3 groups: rosiglitazone group, vehicle (dimethylsulphoxide, DMSO) group and sham operation group. The hepatic samples were collected when mice were sacrificed 0, 2, 4 and 6 h after reperfusion following 1 h ischemia to analyze the acute phase of hepatic IRI. The dynamic expression of TIR4 mRNA was detected quantitatively by real-time-PCR, and the levels of TNF-alpha, IL-10 and ALT in portal vein were determined in all groups. After restoration of blood supply, the expression of TLR4 mRNA in ischemic lobes was detected in 0, 2, 4 and 6 h after reperfusion following 1 h ischemia in rosiglitazone group and vehicle group. The most intensive expression of TLR4 mRNA was present at 4 h after reperfusion in ischemic lobes in vehicle group. As compared with vehicle group, the expression of TLR4 mRNA in ischemic lobes in rosiglitazone group was significantly decreased at 4 h after reperfusion. The level of IL-10 in portal vein was markedly up-regulated in rosiglitazone group as compared with vehicle group. Contrarily, the levels of TNF-alpha and ALT in portal vein were markedly down-regulated in rosiglitazone group as compared with vehicle group at every time point in mouse partial hepatic IRI model. Rosiglitazone could alleviate the hepatic IRI by inhibiting TLR4 receptor-mediated inherent immune response.
Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zhdsh999@163.com
Dongsheng
D
Zhai
Jinxiang
J
Zhang
Qichang
Q
Zheng
Zhengliang
Z
Li
Jinhui
J
Zhang
Yuan
Y
Tian
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D008024:Ligands; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077154:Rosiglitazone