Chinese Hepatolgy ›› 2022, Vol. 27 ›› Issue (1): 33-37.

• Drug-Induced Liver Injury • Previous Articles     Next Articles

Improvement effect of polygoni multiflori radix praeparatac in PD-1 knockout mice with liver injury induced by anti-CTLA-4

WANG Yu1, ZHANG Chun-pan2, WANG Yan1, LIU Li-wei1, LI Ke-xin1, MA Zi-kun1, JIA Ji-dong1, WANG Jia-bo3, ZHAO Xin-yan1   

  1. 1. Liver Research Center,Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases,Beijing 100050, China;
    2. Department of Infectious Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
    3. School of Chinese Medicine, Capital Medical University, Beijing 100069, China
  • Received:2021-11-13 Online:2022-01-31 Published:2022-02-11
  • Contact: ZHAO Xin-yan, Email: zhao_xinyan@ccmu.edu.cn; WANG Jia-bo, Email: jiabo_wang@ccmu.edu.cn

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Abstract: Objective To investigate the effects of the polygoni multiflori radix praeparata (PMRP) in programmed-cell-death-1 (PD-1) knockout mice with liver injury induced by anti-cytotoxic-T-lymphocyte-associated protein-4 (anti-CTLA-4) and its immunological mechanisms.Methods C57BL/6-PD-1-/- mice (n=10) were divided into the control group (n=4) and the PMRP group (n=6). Anti-CTLA-4 was injected intraperitoneally 3 days before experiment, 1 day before experiment and once a week after the experiment started. Normal saline and PMRP were respectively given to the control group and PMRP group with gastric infusion for 42 days. Blood and liver samples were collected on the 43th day, then hematoxylin-eosin (H&E), staining, immunohistochemical stains (IHC) and flow cytometry were performed.Results Compared with the control group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the PMRP group showed a decreased tendency (43.2±15.5 vs 32.8±6.7, P=0.216 and 32.3±7.5 vs 23.8±14.1, P=0.315, respectively). Pathological features of the control group were the existence of multiple inflammatory necrotic foci, macrophages and CD4+ T cells were the main infiltrating cells. The number of inflammatory necrotic foci in the PMRP group [121.5(104.0,147.3) vs 24(17.5,61.5), P=0.014] was significantly lower, the numbers of macrophages and CD4+ T cells were also significantly decreased. Compared with control group, flow cytometry showed that the proportions of macrophages (2.39±0.77% vs 1.37±0.28%, P=0.028) and neutrophils (0.58±0.11% vs 0.34±0.14%, P=0.025) were significantly decreased in PMRP group. The proportion of neutrophils secreting TNF-α significantly decreased in PMRP group (30.15±10.69% vs 11.56±6.05%, P=0.012). Compared with control group, the proportions of CD4+ T and CD8+ T cells did not change significantly, however the proportions of activated CD4+ T cells and CD8+T cells which secreted granzyme B significantly decreased in the PMRP group (26.20±3.47% vs 16.74±6.95%, P=0.044 and 77.05±4.23 % vs 59.70±10.81%, P=0.020, respectively).Conclusion PMRP can improve liver function in PD-1-/- mice with liver injury induced by anti-CTLA-4, the mechanisms are inhibiting macrophages recruitment, neutrophils and effective T cells activation.

Key words: Polygonum multiflorum radix praeparato, Programmed-cell-death-1, Cytotoxic-T-lymphocyte-associated protein-4, Immune cells infiltration, Macrophages, CD4+T cells