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Volume 42 Issue 3
Mar.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(3): 600-607

Effect of sitravatinib on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism

DOI: 10.12449/JCH260315
  • 1.

    Department of Infectious Diseases，Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine，Nanjing 210008，China

  • 2.

    Department of Infectious Diseases，Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School，Nanjing University，Nanjing 210008，China

Research funding:

Beijing iGandan Foundation (iGandanF-1082024-LG004);

Beijing iGandan Foundation (iGandanF-1082025-LG034);

Beijing iGandan Foundation (iGandanF-1082025-LG019);

Nanjing Drum Tower Hospital Clinical Research Special Fund Project (2024-LCYJ-PY-52);

Nanjing Drum Tower Hospital Clinical Research Special Fund Project (2025-LCYJ-PY-02);

Nanjing Drum Tower Hospital Youth Cultivation Fund (2025-JCYJ-QP-016);

Nanjing Drum Tower Hospital Youth Cultivation Fund (2025-JCYJ-QP-017);

Project of Institute of Chinese Medicine, Nanjing University and Aid Project of Nanjing Drum Tower Hospital Health, Education & Research Foundation (ICM2024002);

Project of Institute of Chinese Medicine, Nanjing University and Aid Project of Nanjing Drum Tower Hospital Health, Education & Research Foundation (ICM2024032);

China Postdoctoral Science Foundation (2024M761417)

More Information
  • Corresponding author: LI Jie， lijier@nju.edu.cn （ORCID： 0000-0003-0973-8645）
  • Received Date: 2025-09-15
  • Accepted Date: 2026-01-15
  • Published Date: 2026-03-25
    Abstract
  •   Objective  To investigate the therapeutic effect of sitravatinib on carbon tetrachloride （CCl4）-induced liver fibrosis in mice.  Methods  A total of 30 male C57BL/6J mice， aged 8 weeks， were randomly divided into control group， CCl4 model group， and low- （5 mg/kg）， middle- （10 mg/kg）， and high-dose （20 mg/kg） sitravatinib groups. All mice except those in the control group were given intraperitoneal injection of CCl4 for 4 consecutive weeks to induce liver fibrosis， and since the first day of modeling， the mice in the low-， middle-， and high-dose sitravatinib groups were given sitravatinib at the corresponding dose by gavage every day. The serum levels of total cholesterol （TC）， triglyceride （TG）， and alanine aminotransferase （ALT） were measured for the mice in each group； hepatic hydroxyproline content was measured； HE staining， Masson staining， and Sirius Red staining were used to observe liver histopathological changes； quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of α-smooth muscle actin （α-SMA） and collagen type I alpha 1 （Col1a1） in liver tissue. The therapeutic effect of sitravatinib was assessed based on the above results. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups.  Results  Compared with the control group， the model group had significant increases in the levels of TC， TG， and ALT （all P<0.05）， and there were no significant differences in the levels of TC， TG， and ALT between the model group and the low-， middle-， and high-dose sitravatinib groups （all P>0.05）. Hepatic hydroxyproline content decreased after sitravatinib intervention， with a significant difference between the middle-/high-dose sitravatinib groups and the CCl4 model group （both P<0.05）. Histopathological staining showed that the sitravatinib treatment groups had a reduction in collagen deposition， along with thinning and fragmentation of fibrous septa， and in the high-dose sitravatinib group， 4 mice had a fibrosis stage of S0—S1 and 2 mice had a fibrosis stage of S2—S3， suggesting a certain degree of alleviation of liver fibrosis degree compared with the CCl4 model group （mainly S3—S4）. The measurement of related molecules showed that sitravatinib downregulated the mRNA and protein expression levels of α-SMA and Col1a1 （all P<0.05）.  Conclusion  Sitravatinib can effectively alleviate CCl4-induced liver fibrosis in mice， possibly by inhibiting hepatic stellate cell activation and collagen synthesis.

     

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