The Effect And Mechanism Of Resveratrol On Apoptosis Of T-cell Acute Lymphoblastic Leukemia In Mice

Objective:According to the effect of resveratrol on apoptosis of mouse with T-cell acute lymphoblastic leukemia(T-ALL)to elucidate the mechanism of apoptosis of resveratrol against T-ALL by analyzing the apoptosis-related protein expression of Bcl-2/Bax and P53.Methods:1.Experimental Grouping:Eighteen female C57BL/6 mice were randomly divided into 3 groups:normal control group(Con group),T-ALL model control group(Model group)and resveratrol(100 mg/kg/d)treatment group(Res group).Mouse model of T-ALL leukemia was established by being injected with 0.2 ml of 5×10 ~6/ml leukemia cells overexpressing ICN1~-GFP~+through the tail vein of mice.2.Morphological changes of peripheral blood cells were examined by Wright-Giemsa staining in mice of each group.3.Pathological morphology changes of spleen,liver,kidney and bone marrow tissues were examined by HE staining in mice of each group.4.The leukemia cell rate and apoptotic rate of peripheral blood cells were measured by flow cytometry(FCM)in mice of each group5.The mRNA expressions of Bax,Bcl-2 and P53 of spleen were detected by Real-time quantitative PCR(RT-PCR)in mice of each group.6.The protein expression levels of Bax,Bcl-2 and P53 of spleen were tested by Western Blot in mice of each group.Results:1.The results of peripheral blood smear by Wright-Gemsa staining showed that the lymphoblasts were increased in model group.The percentages of leukemia cells in Res group were significantly lower than that in Model group(P<0.05).2.The results of pathological morphology by HE staining showed that the spleen,liver,kidney and bone marrow tissues were infiltrated diffusely with leukemia cells in model group.The degree of leukemia cell infiltration in Res group was significantly less than that in model group.3.Compared with model group,the leukemia cell rates of the peripheral blood were decreased significantly in Res group(P<0.05),and the apoptotic rates of leukemia cell were significantly increased(P<0.05).4.Compared with the Control group,the relative mRNA expressions of Bax and P53 of spleen in model group were significantly down-regulated using RT-PCR(P<0.05),and Bcl-2 mRNA expressions were significantly increased(P<0.05).After treatment with Res,the Bax and P53 mRNA expressions of the spleen were significantly increased(P<0.05),and the Bcl-2mRNA expressions were significantly decreased(P<0.05).5.Compared with the control group,the protein expressions of Bax and P53 of spleen in model group were significantly down-regulated(P<0.05),and the Bcl-2 protein expressions were significantly increased(P<0.05).After treatment with Res,the protein expressions of Bax and P53 were significantly increased(P<0.05),and Bcl-2 expressions were significantly decreased(P<0.05).Conclusion:Resveratrol can significantly improve the degree of leukemia cell infiltration into various tissues of T-ALL mice,and have an anti-T-ALL effect by enhanceing leukemia cell apoptosis,which may be related to the inhibition of anti-apoptosis Bcl-2 protein and the promotion the proapoptotic protein expressions of Bax and P53.