Significance of Rosiglitazone Inhibiting TLR4 Expression in Partial Hepatic Ischemia/Reperfusion of Mice
10.1007/s11596-008-0516-8
- Author:
ZHAI DONGSHENG
1
,
2
;
ZHANG JINXIANG
;
ZHENG QICHANG
;
LI ZHENGLIANG
;
ZHANG JINHUI
;
TIAN YUAN
Author Information
1. Department of General Surgery, Wuhan 430022, China
2. Department of General Surgery, Affiliated Hospital of Hubei Institute for Nationalities, Enshi 445000, China
- Keywords:
hepatic reperfusion injury;
toll-like receptor;
rosiglitazone;
peroxisome proliferator-activated receptorγ
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2008;28(5):564-567
- CountryChina
- Language:Chinese
-
Abstract:
Summary: The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptorγ (PPARγ) inhibiting the TLR4 expression in ischemic lobes in partial hepatic ischemia/reperfusion injury (IRI) in BABL/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 1h ischemia to analyze the acute phase of hepatic IRJ. The dynamic expression of TIR4 mRNA was detected quantitatively by real-time-PCR, and the levels of TNF-α, 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 6h after reperfusion following 1h 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 4h 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-α 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.
