STAT3 在对乙酰氨基酚所致小鼠肝损伤后肝细胞再生中的作用.

Objective To investigate the role of STA TI in hepatocyte proliferation after acetaminophen ( APAP) - induced hepatocellular injury in mice. Methods Normal mouse AML12 hepatocytes were cultured in vitro and were stimulated by APAP ( 1, 2. 5, 5, 10, and 20 mmoVL) for 12, 24 or 48 hours, and the hepatocytes treated with an equal volume of phosphate buffered saline were established as control group. After the optimal stimulation concentration and duration of action were screened out, AML12 hepatocytes were treated with AG490 (10, 50, and 100 µ,moVL). The CCK - 8 assay was used to measure the viability of AML12 hepatocytes; RT - PCR was used to measure the mRNA expression levels of PCNA, CyclinDl, and Ki67 in AML12 hepatocytes, and Western blot was used to measure the protein expression levels of STA TI, p - STA TI, PCNA, and CyclinDl. A one - way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t - t est was used for further comparison between two groups. Results After 24 and 48 hours of APAP treatment, compared with the control group, all concentration groups had a significant reduction in the viability of AML12 hepatocytes ( all P <0. 05), with a viability of 0. 717 ± 0. 0271 and 0. 752 ± 0. 0141, respectively, when the concentration of APAP was 2. 5 mmoVL, which was significantly different from that in the control group ( all P < 0. 05 ) and met the conditions of subsequent experiment. Compared with the control group, the 24 - hour APAP ( 2. 5 mmol/L) group had significant reductions in the mRNA expression of PCNA, CyclinDl, and Ki67 ( all P < 0. 01) ; compared with the 24 - hour APAP group, the 48 - hour APAP ( 2 . 5 mmoVL) group had significant increases in the mRNA expression of PCNA, CyclinDl, and Ki67 (all P <0. 01); therefore, a model of hepatocyte regeneration after in vitro AML12 hepatocyte injury was established by stimulation with APAP 2. 5 mmoVL for 48 hours. After the addition of AG490, there was no significant difference in viability between the control group and the 10 and 50 µ,moVL AG490 groups, and the other groups had a sigChemical and Drug Induced Liver Injury; STA TI transcription factor; Acetaminophen; Liver Regeneration. [ABSTRACT FROM AUTHOR]