Significance of rosiglitazone inhibiting TLR4 expression in partial hepatic ischemia/reperfusion of mice
Significance of rosiglitazone inhibiting TLR4 expression in partial hepatic ischemia/reperfusion of mice
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DOI：
10.1007/s11596-008-0516-8
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发表时间：
2008-10
期刊：
影响因子：
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通讯作者：
Dongsheng Zhai;Jinxiang Zhang;Qi-chang Zheng;Zhengliang Li;Jin-hui Zhang;Yuan Tian
中科院分区：
文献类型：
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作者：
Dongsheng Zhai;Jinxiang Zhang;Qi-chang Zheng;Zhengliang Li;Jin-hui Zhang;Yuan Tian
为探讨罗格列酮作为过氧化物酶体增殖物激活受体γ(PPARγ)配体对BABL/C小鼠部分肝缺血再灌注损伤缺血叶TLR4表达的抑制作用，以及罗格列酮对TLR4受体介导的固有免疫反应的抑制作用。建立小鼠部分肝缺血再灌注损伤模型。实验动物随机分为3组：罗格列酮组、赋形剂(二甲基亚砜)组和假手术组。分别于缺血1h再灌注0、2、4、6h处死小鼠，取肝脏标本进行肝脏IRI急性期分析。实时定量检测TIR4mRNA的动态表达，检测各组门静脉血中肿瘤坏死因子α、白介素10和丙氨酸氨基转移酶的水平。罗格列酮组和赋形剂组在血供恢复后，缺血1h再灌流后0、2、4、6h分别检测缺血叶TLR4mRNA的表达。赋形剂组脑缺血区TLR4mRNA在再灌流后4h表达最强。再灌注4h，罗格列酮组缺血叶TLR4mRNA表达明显低于假手术组。罗格列酮组大鼠门静脉血中IL-10水平较空白对照组明显升高。相反，在小鼠部分肝缺血再灌注模型中，罗格列酮组各时间点门静脉血中肿瘤坏死因子-α和丙氨酸氨基转移酶水平均明显低于空白对照组。罗格列酮可能通过抑制TLR4受体介导的固有免疫反应而减轻肝脏IRI。
The effect of rosiglitazone as the ligand of peroxisome proliferator-activated receptor γ (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 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-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 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-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.