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Effect of Hirudin on farnesol X receptor pathway during acute intrahepatic cholestasis

  • Yu-Qing Liu1,
  • Yao Wang2,
  • Wen-Qian Tang1,
  • Xin Cai1,
  • Ren-Wu Qin3,
  • Lei Luo4 and
  • Fan Yang5,*
 Author information 

Abstract

Objective

The purpose of this study is to explore the effect of Hirudin on the farnesoid X receptor (FXR) pathway during acute intrahepatic cholestasis in vivo and in vitro.

Method

In vivo, sixty male Sprague-Dawley rats were randomly divided into six groups: regular group, model group, ursodeoxycholic acid (UDCA) group (60 mg/kg), hirudin treatment group (84 u/kg), hirudin treatment group (63 u/kg) and hirudin treatment group (42 u/kg).The male Sprague-Dawley rats of UDCA group were intragastrically administered with a corresponding concentration of 0.005 mL/g body weight for seven days, once a day; and the hirudin treatment group was injected subcutaneously with different concentrations of Hirudin for seven days, once a day; Except for the normal group, other groups of rats were given 100 mg/kg ANIT by gavage on the 5th day. The model was administered by gavage once a day for three days. In vitro, (Z)-Guggulsterone was used to stimulate the L02 cells (0.05 μmol/ml), with or without different concentrations of Hirudin (2, 4 and 8 u/ml) for 24 h. The liver tissue was examined by HE microscope and the pathological state of the rat liver was observed; FXR, Small heterodimeric chaperone receptor (SHP), uridine diphosphate glucuronide transfer 2B4 (UGT2B4), bile salt output pump (BSEP)mRNA and protein expressions were tested by real-time fluorescent quantitative PCR and Western blot test. And immunohistochemistry (IHC) was used to analyze the expression of FXR.

Results

Compared with the model group, the hirudin group can improve liver tissue damage, and promote FXR, SHP, BSEP and UGT2B4 proteins and mRNA expression in vivo and in vitro.

Conclusion

Hirudin can alleviate intrahepatic cholestasis, reduce liver tissue damage. Hirudin can up-regulate the expression of FXR gene, promote the up-regulation of SHP, BSEP and UGT2B4 genes, and inhibit the cholestasis pathway to protect liver cells. The study may provide an effective drug for clinical treatment of intrahepatic cholestasis.

Keywords

hirudin, (Z)-Guggulsterone, α-isothiocyanate (ANIT), cholestasis, FXR

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Liu YQ, Wang Y, Tang WQ, Cai X, Qin RW, Luo L, et al. Effect of Hirudin on farnesol X receptor pathway during acute intrahepatic cholestasis. Gastroenterol & Hepatol Res. 2022;4(2):10. doi: 10.53388/ghr2022-06-052.
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Article History
Received Revised Accepted Published
June 30, 2022
DOI http://dx.doi.org/10.53388/ghr2022-06-052
  • Gastroenterology & Hepatology Research
  • eISSN 2703-173X
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Effect of Hirudin on farnesol X receptor pathway during acute intrahepatic cholestasis

Yu-Qing Liu, Yao Wang, Wen-Qian Tang, Xin Cai, Ren-Wu Qin, Lei Luo, Fan Yang
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