高迁移率族蛋白B1在小鼠肝再生中对细胞增殖的作用及机制

doi:10.3969/j.issn.1004-616x.2020.02.001

Abstract

Abstract: OBJECTIVE: To study the effect and regulatory mechanism of high-mobility group box 1 (HMGB1) on cellular proliferation during liver regeneration after partial hepatectomy (PH) in mice. METHODS: Using the classic mouse model of 70% PH,21 male BALB/c mice were randomly divided into the sham operation and the six PH groups (n=3). Mice in the sham operation group, the abdominal cavities were open surgically to expose but without removal of the liver,while mice in the PH group received 70% PH and were killed at 6 h,and at 1,2,3,5 and 7 days after the operation,respectively. In addition,ethyl pyruvate (EP) was used as the specific inhibitor of HMGB1 for intervention. In this experiment,9 male BALB/c mice were randomly divided into sham operation,PH and ethyl pyruvate (EP) intervention (n=3) groups. Mice in EP intervention group were intraperitoneally injected with EP at 40 mg/(kg·d) after 70% hepatectomy,and were killed 2 days after operation. Total protein and nuclear or cytoplasmic proteins were extracted from liver tissues of mice from each group,and the protein expression levels of HMGB1,TLR4,RAGE,NF-κB p65,Cyclin D1 and PCNA were detected by Western blot. RESULTS: Within one week after mice had PH,the protein expression level of HMGB1 in cellular nuclei reached the peak on the 2nd day after operation (P < 0.05),then decreased gradually. Changes of protein expression levels in the cytoplasm was consistent with that trend. In addition,the protein expression levels of TLR4,RAGE,NF-κB p65,Cyclin D1 and PCNA in the PH group were also significantly higher than those in the sham operation group (P < 0.05). After the intervention of EP,the expression levels of HMGB1 in the nuclear protein of liver tissues and the expression levels of TLR4 and RAGE in the total protein did not change significantly. However,the expression levels of HMGB1 in the cytoplasmic protein and the protein expression levels of NF-κB p65,Cyclin D1 and PCNA decreased significantly (P < 0.05). CONCLUSION: HMGB1 played a regulatory role in cellular proliferation during mice liver regeneration,and this protein may be used as a potential important intervention target for the regulation of liver regeneration.

Key words: high-mobility group box 1, ethyl pyruvate, partial hepatectomy, liver regeneration, cellular proliferation

CLC Number:

FANG Congwen, SHI Ying, DU Feng, KANG Bingwen, HAN Mingbo, YIN Caocao, BAI Hua, QIN Xujun. Involvement of high-mobility group box 1 in cellular proliferation during liver regeneration in mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 81-86.

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Involvement of high-mobility group box 1 in cellular proliferation during liver regeneration in mice

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