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Significance of rosiglitazone inhibiting TLR4 expression in partial hepatic ischemia/reperfusion of mice

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Summary

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.

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Authors and Affiliations

  1. Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Dongsheng Zhai  (翟东升), Qichang Zheng  (郑启昌), Zhengliang Li  (李铮良), Jinhui Zhang  (张锦辉) & Yuan Tian  (田 元)

  2. Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Jinxiang Zhang  (张进祥)

  3. Department of General Surgery, Affiliated Hospital of Hubei Institute for Nationalities, Enshi, 445000, China

    Dongsheng Zhai  (翟东升)

Authors
  1. Dongsheng Zhai  (翟东升)
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  2. Jinxiang Zhang  (张进祥)
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  3. Qichang Zheng  (郑启昌)
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  4. Zhengliang Li  (李铮良)
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  5. Jinhui Zhang  (张锦辉)
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  6. Yuan Tian  (田 元)
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Additional information

This project was supported by a grant from National Natural Sciences Foundation of China (No. 30200272).

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Zhai, D., Zhang, J., Zheng, Q. et al. Significance of rosiglitazone inhibiting TLR4 expression in partial hepatic ischemia/reperfusion of mice. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 28, 564–567 (2008). https://doi.org/10.1007/s11596-008-0516-8

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  • DOI: https://doi.org/10.1007/s11596-008-0516-8

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