首页|白藜芦醇抑制Notch1信号通路对抗小鼠急性T淋巴细胞白血病

白藜芦醇抑制Notch1信号通路对抗小鼠急性T淋巴细胞白血病

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目的:观察白藜芦醇(Res)对急性T淋巴细胞白血病(T-ALL)小鼠的影响,并进一步探讨其对Notch1信号通路的作用机制.方法:将25只6-8周龄雌性C57BL/6小鼠随机分为正常对照组、T-ALL组和Res组,其中Res组又进一步分为low-Res(L-Res)、middle-Res(M-Res)和high-Res(H-Res)3个浓度给药组.应用流式细胞术和瑞氏-吉姆萨染色法检测外周血及脾细胞悬液中白血病细胞百分比,HE染色法观察脾脏和骨髓组织病理形态,RT-qPCR法检测脾脏组织中 Notch1、Hes-1、c-Myc、miR-19b 和 PTEN mRNA 表达水平,Western blot 法检测 Notch1、Hes-1、c-Myc、p-PTEN和PTEN蛋白表达水平.结果:与对照组相比,T-ALL组小鼠外周血中白血病细胞明显增多,脾脏及骨髓组织中白血病细胞弥漫性浸润,脾脏中Notch1、Hes-1、c-Myc、miR-19b mRNA表达水平和Notch1、Hes-1、c-Myc蛋白表达水平均明显增高(P<0.01),PTEN mRNA及其蛋白水平显著降低(P<0.01),经白藜芦醇处理后,H-Res组以上各项指标较T-ALL组均获得逆转.结论:白藜芦醇具有抗小鼠T-ALL的作用,其机制可能通过抑制Notch1信号通路发挥作用.
Resveratrol Inhibits T-acute Lymphoblastic Leukemia in Mice by Regulating Notch1 Signaling Pathway
Objective:To observe the effect of resveratrol(Res)on T-acute lymphoblastic leukemia(T-ALL)mice,and further explore its mechanism on Notch1 signaling pathway.Methods:Twenty-five 6-8 weeks old female C57BL/6 mice were randomly divided into control group,T-ALL group and Res group.Res group was further divided into low-Res.middle-Res and high-Res group.The percentage of leukemia cells in peripheral blood and spleen cell suspension were detected by flow cytometry and Wright-Giemsa staining,pathological morphology of spleen and bone marrow tissues were observed by HE staining,the expression levels of Notch1,Hes-1,c-Myc,miR-19b and PTEN mRNA in spleen tissue were detected by RT-qPCR,and the protein levels of Notch1,Hes-1,c-Myc,p-PTEN and PTEN were detected by Western blot.Results:Compared with control group,the leukemia cells in peripheral blood of mice in T-ALL group were markedly increased,accompanied by diffuse infiltration of leukemia cells in spleen and bone marrow tissues,the mRNA levels of Notch1,Hes-1,c-Myc,miR-19b and the protein levels of Notch1.Hes-1,c-Myc were increased(P<0.01),while the expression of PTEN mRNA and protein were significantly decreased in the spleen tissue of T-ALL mice(P<0.01).The above indicators in the H-Res group were reversed compared with T-ALL group after administration of resveratrol.Conclusion:Resveratrol may play a role in anti T-ALL by inhibiting Notch1 signaling pathway in mice.

resveratrolT-acute lymphoblastic leukemiaNotch1 signaling pathwaymice

李晓菲、崔芳、刘菲、张瑞、史敏、李永军

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河北医科大学第二医院检验科,河北石家庄 050000

河北医科大学电镜实验中心,河北石家庄 050017

白藜芦醇 急性T淋巴细胞白血病 Notch1信号通路 小鼠

河北省自然科学基金

H2020206396

2024

中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCD北大核心
影响因子:0.988
ISSN:1009-2137
年,卷(期):2024.32(1)
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