The Effect Of Resveratrol On Mouse With Acute T Lymphocytic Leukemia And The Mechanism Of Notch1 Signaling Pathway

Objective:To observe the effect of resveratrol on acute T-lymphocytic leukemia mice and the expression levels of Notch1 and Hes-1 signaling molecules,and to explore the mechanism of action.Methods:1.50 C57BL/6 female mice were divided into 5 groups completely by randomization:normal control group;model control group;Resveratrol low-dose treatment group(25mg/kg/d);Resveratrol medium-dose treatment group(50mg/kg/d);Resveratrolhigh-dosetreatmentgroup(100mg/kg/d).1×10~6 leukemia cells were injected into C57BL/6 mice by tail vein to prepare an acute T lymphocyte leukemia model.2.Swiss-Gimsa staining was used to observe the infiltration of leukemic cells in peripheral blood of each group.3.The percentage of leukemia cells in the peripheral blood and spleen cell suspensions of each experimental group was detected by flow cytometry.4.HE staining was used to observe the infiltration of leukemia cells in the liver,spleen,kidney and bone marrow of each experimental group.5.Application of real-time fluorescence quantitative PCR(RT-PCR)to detect the expression levels of Notch1,Hes-1 mRNA in spleen tissues of each group.6.Western blot was used to detect the expression levels of Notch1 and Hes-1 protein in spleen tissues of each group.Results:1.Primitive lymphocytes were observed in peripheral blood smears of each group,and the nucleus were round or slightly oval,also were large and deep staining,and the chromatin is dense;the leukocyte count results show that the proportion of leukemia cells in the model group is significantly increased,the proportion of leukemia cells in the low,medium and high concentrations of resveratrol group was significantly reduced(P<0.05),as the concentration of resveratrol increased,the proportion of peripheral blood leukemia cells gradually decreased;2.Flow cytometry detection of peripheral blood showed that the percentage of leukemia cells in the medium and high concentration treatment group of resveratrol was significantly reduced compared with the model control group(P<0.05);The results of spleen cell suspension showed that the percentage of leukemia cells in the high resveratrol treatment group was significantly reduced compared with the model control group(P<0.05);3.The results of HE staining showed that resveratrol significantly inhibited the infiltration of leukemia cells into liver,kidney and bone marrow tissues.When the concentration of resveratrol increases,the number of leukemia cells gradually decreases;4.The RT-PCR results showed that compared with the model control group,the high concentration of resveratrol significantly down-regulated the expression of Notch1 gene(P<0.05);5.Western results showed that compared with the model control group,high concentrations of resveratrol significantly down-regulated the expression of Notch1 protein(P<0.05);The expression of Hes-1 protein was significantly decreased in the medium and high concentrations of resveratrol treatment group compared with the model control group(P<0.05).Conclusions:Resveratrol has the effect of on acute T lymphoblastic leukemia in mice and might play a role by inhibiting Notch1 signaling pathway.