title: [Association between protective effect of Liuwei Wuling tablets against acute liver injury and its inhibitory effect on cytoplasmic translocation of high-mobility group box-1 in hepatocytes in mice].
abstract: OBJECTIVE
  To investigate the effect of Liuwei Wuling tablets on the cytoplasmic translocation and release of high-mobility group box-1 (HMGB1) in hepatocytes in mice with acute live injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS).
  
  
  METHODS
  A Balb/c mouse model of acute liver injury was established by intraperitoneal injection of D-GalN (400 mg/kg) and LPS (5 ug/kg). A total of 24 healthy mice were randomly and equally divided into acute liver injury control group and Liuwei Wuling tablet treatment group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in both groups at each time point within one week. Liver tissues were collected at 36 hours to perform pathological examination. The serum levels of HMGB1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), complement 3a (C3a), and complement 5a (C5a) were measured. Immunohistochemistry was used to determine the expression and cytoplasmic translocation of HMGB1 in hepatocytes.
  
  
  RESULTS
  At 6, 12, and 24 hours, the Liuwei Wuling tablet treatment group had significantly lower serum levels of ALT than the control group (225.33±181.64 U/L vs 471.17±174.72 U/L, t = 3.38, P < 0.01; 1509.53±182.51 U/L vs 7149.52±734.25 U/L, t = 25.82, P < 0.01; 162.89±86.51 U/L vs 1318.16±557.71 U/L, t = 7.09, P < 0.01), as well as significantly lower serum levels of AST than the control group (179.22±94.57 U/L vs 561.91±209.6 U/L, t = 5.76, P < 0.01; 590.92±190.92 U/L vs 2266.48±705.64 U/L, t = 7.94, P < 0.01; 231.24±87.7 U/L vs 444.32±117.01 U/L, t = 5.05, P < 0.01). The treatment group had significantly lower levels of HMGB1 than the control group at 6 and 12 hours (54.21±11.89 ng/ml vs 72.07±13.65 ng/ml, t = 3.41, P < 0.01; 49.23±5.97 ng/ml vs 68.71±13.07 ng/ml, t = 4.70, P < 0.01). The treatment group had significantly lower levels of TNF-α, IL-1β, and IL-6 than the control group at 12 hours (163.62±9.12 pg/ml vs 237.09±51.47 pg/ml, t = 4.86, P < 0.01; 15.66±13.13 pg/ml vs 37.43±18.68 pg/ml, t = 3.30, P < 0.01; 7.10±3.06 pg/ml vs 21.42±8.23 pg/ml, t = 5.65, P < 0.01). The treatment group had significantly lower levels of C3a and C5a than the control group at 12 hours (2.52±1.27 pg/ml vs 9.83±2.96 ng/ml, t = 7.86, P < 0.01; 2.16±1.03 ng/ml vs 7.23±1.55 ng/ml, t = 9.67, P < 0.01). Compared with the control group, the treatment group had significantly reduced liver inflammation and necrosis, and a significantly lower cytoplasmic translocation rate of HMGB1 in hepatocytes (38.76%±7.37% vs 8.15%±2.11%, P < 0.01).
  
  
  CONCLUSIONS
  Liuwei Wuling tablets can reduce the cytoplasmic translocation of HMGB1 in hepatocytes and relieve liver inflammation in mice with acute liver injury.
authors.affiliation: Department of Infectious Diseases, Zhejiang Hospital, Hangzhou 310013, China.
authors.forename: Yangchang
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Affiliated Infectious Disease Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Affiliated Infectious Disease Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Luo
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015926:Complement C3a / Q000032:analysis; D015936:Complement C5a / Q000032:analysis; D003593:Cytoplasm / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005688:Galactosamine; D024243:HMGB1 Protein / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013607:Tablets; D014409:Tumor Necrosis Factor-alpha; C000605969:liuweiwuling; D005688:Galactosamine; D015926:Complement C3a; D015936:Complement C5a; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase