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白藜芦醇通过调节Notch1信号通路抑制小鼠T急性淋巴细胞白血病

[Resveratrol Inhibits T-acute Lymphoblastic Leukemia in Mice by Regulating Notch1 Signaling Pathway].

作者信息

Li Xiao-Fei, Cui Fang, Liu Fei, Zhang Rui, Shi Min, Li Yong-Jun

机构信息

Department of Clinical Laboratory Examination, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.

Department of Electron Microscopy Laboratory Center, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Feb;32(1):57-65. doi: 10.19746/j.cnki.issn.1009-2137.2024.01.010.

Abstract

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 and 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 and the protein levels of Notch1, Hes-1, c-Myc were increased ( <0.01), while the expression of mRNA and protein were significantly decreased in the spleen tissue of T-ALL mice ( <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.

摘要

目的

观察白藜芦醇(Res)对T急性淋巴细胞白血病(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小鼠随机分为对照组、T-ALL组和Res组。Res组进一步分为低Res、中Res和高Res组。采用流式细胞术和瑞氏-吉姆萨染色检测外周血和脾细胞悬液中白血病细胞的百分比,通过HE染色观察脾脏和骨髓组织的病理形态,用RT-qPCR检测脾脏组织中相关mRNA的表达水平,采用蛋白质印迹法检测Notch1、Hes-1、c-Myc、p-PTEN和PTEN的蛋白水平。

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,伴有脾脏和骨髓组织中白血病细胞的弥漫性浸润,相关mRNA水平以及Notch1、Hes-1、c-Myc的蛋白水平升高(P<0.01),而T-ALL小鼠脾脏组织中相关mRNA和蛋白的表达明显降低(P<0.01)。给予白藜芦醇后,高Res组上述指标与T-ALL组相比出现逆转。

结论

白藜芦醇可能通过抑制小鼠Notch1信号通路发挥抗T-ALL作用。

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