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  • Title: [Targeting glycyrrhetinic acid to hepatic stellate cells in treating rat liver fibrosis].
    Author: Zhang QS, Luk JM, Zhang J, Tian GY.
    Journal: Zhonghua Gan Zang Bing Za Zhi; 2005 Sep; 13(9):664-7. PubMed ID: 16174454.
    Abstract:
    OBJECTIVES: We synthesized M6P26-HSA as a carrier for hepatic stellate cells (HSC) and coupled it with glycyrrhetinic acid (GA) to get a new conjugate GA-HSA-M6P26. Its organ distribution, specific combination with HSC and anti-fibrotic effect on livers were studied. METHODS: The GA-HSA-M6P26 was labeled with 125I and its organ distribution was detected radiologically. Selective combination of GA-HSA-M6P26 was observed with double immunocytochemic staining and collagen staining of the liver preparations was carried out using Sirius red staining method. The effect of the conjugate on mRNA expression of type I procollagen was studied with real-time PCR in vivo. RT-PCR was used for the effect on mRNA expression of alpha-SMA, MMP-9 and TIMP-1. RESULTS: 10 minutes after GA-HSA-M6P26 i.v. injection, 55%+/-5% of it was distributed in the livers. Double immunocytochemic staining showed that most of GA-HSA-M6P26 was taken up by HSC. With GA- HSA- M6P26 treatment, the collagen deposition in the liver decreased significantly compared with GA and M6P26-HSA treated rats. Similarly, the mRNA expression of type I procollagen and alpha-SMA dropped significantly. As to MMP-9 and TIMP-1, no significant change was shown. CONCLUSION: GA-HSA-M6P26 was selectively delivered to HSC and it showed a significant anti-fibrotic effect on rat liver fibrosis.
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