Résumé
Objective To observe the protective effects of FTY720 on the Con A-induced mouse hepatic fibrosis injury,and to find the possible mechanisms of protective effects.Methods The pathologic models of hepatic fibrosis injury in the mice caused by Con A were set up.Forty mice were randomly divided into control group, model group,high dose of FTY720 (4 mg·kg-1 )group and low dose of FTY720 (1 mg·kg-1 )dose group (n=10).The serum alanine aminotransferase (ALT)and asparate aminotransferase (AST)activities,hepatic index and pathological changes of hepatic tissue were detected .Results Compared with model group,the serum ALT and AST activities in low and high doses of FTY720 groups were decreased significantly (P < 0.05 or P < 0.01).The optical microscope results showed that there were inflammatory cells and hepatocellular necrosis in model group. The masson staining results showed that there were surrounding fiber bundle and hepatic lobule fusion in model group;compared with model group,the damage degree in low and high doses of FTY720 groups was reduced.The protective effects of FTY720 on hepatic injury showed linear relation to the drug dose.Conclusion FTY720 could decrease the levels of ALT/AST,thus FTY720 alleviate hepatic damage degree and delay the process of hepatic fibrosis.The protective effects of FTY720 on hepatic injury in experimental hepatic fibrosis mice may be related to the mechanisms mentioned above.
Résumé
Objective To study the apoptosis of K562 cells induced by a new immunosuppressive agent FTY720 and its mechanism,and to provide experimental basis for the treatment of leukemia in clinic.Methods The K562 cells were cultured in vitro and divided into blank control group and FTY720 treatment group.The K562 cells in FTY720 treatment group were treated with 6μmol·L-1 FTY720 for 3,6,and 12 h,or treated with different concentrations of FTY720 (2,4,6,8μmol·L-1)for 24 h.The apoptosis,level of reactive oxygen species (ROS),mitochondrial membrane potential(MMP)and cell cycle were measured by flow cytometry.The inhibitory rate of proliferation of K562 cells after treated with FTY720 was detected by WST-1 reducting assay.Results The results of flow cytometry showed that the percentages of apoptotic cells were increased after treated with 6μmol·L-1 FTY720 for 3,6,and 12 h with the prolongation of time compared with blank control group(P<0.01).The percentages of apoptotic cells were also increased after treated with different concentrations of FTY720 for 24 h compared with blank control group(P<0.01).Compared with blank control group,the ROS levels were increased with the increasing of FTY720 concentration,while the MMP was decreased(P<0.01).Compared with blank control group,the percentage of cells at G0/G1 phase was increased,while those at S and G2/M phases were decreased with the increasing of FTY720 concentration (P<0.05).The WST-1 reduction assay results indicated that the inhibitory rates of proliferation of K562 cells after treated with 2,4,6,and 8μmol·L-1 FTY720 for 72 h were (24.0±4.1)%,(46.4±3.9)%,(67.0±4.8)%,and (88.2±5.6)%,respectively,compared with blank control group.The concentration of FTY720 to result the inhibitory rate of 50% (IC50 )on K562 cells was 5.5μmol·L-1 .Conclusion FTY720 could inhibit the proliferation of K562 cells by blocking cell cycle and inducing apoptosis through provoking ROS.
Résumé
Two decolorizing agents for formalin-fixed skin have been studied, of which one is a mixture of Ac_2O, H_2O_2, KOAc, and EDTA, and the other, a mixture of H_2O_2, KOAc, and EDTA. These decolorizing agents possess stronger decolorizing ability and are less damageable to skin than commonly used aqueous H_2O_2, solution. The reactions between the decolorizing agents and keratin in epidermis have been revealed by X-ray photoelectron spectroscopy to be mainly oxidation of the disulfide linkage of cystine to sulfonate group.