摘要
目的 探讨芹糖异甘草苷(ILA)在体内通过影响免疫系统对小鼠认识水平和抗肿瘤作用的影响。方法 尾静脉注射的方式给小鼠注射ILA;采用水迷宫检测小鼠的认知水平;流式细胞术检测免疫细胞T细胞、B细胞、NK细胞的数量;利用重度免疫缺陷鼠B-NDG进行免疫重建观察ILA与免疫系统的关系;检测脾脏组织免疫细胞T细胞、B细胞、NK细胞数量;B-NDG小鼠血液和海马组织进行RNA测序分析ILA调控的相关信号通路;采用CCK-8法体外检测人宫颈癌细胞活性,初步探讨ILA与肿瘤之间的联系。结果 水迷宫结果表明ILA不能改善小鼠的认知能力。流式细胞术检测免疫细胞中的T细胞、B细胞、NK细胞数量,结果表明ILA能稳定增加正常小鼠血液(P<0.01)和脾脏组织(P<0.01)中NK细胞的数量,ILA能增加重度免疫缺陷小鼠脾脏组织中的NK细胞数量并促进NK细胞的重建(P<0.01)。B-NDG小鼠血液RNA测序结果表明,ILA调控血小板激活、病灶黏附、趋化因子信号通路以及FcγR介导的吞噬凋亡作用,在血小板激活通路中上调Snap23、Rap1b、Fcer1g、Fermt3、p2ry12、Gnai2基因。B-NDG小鼠海马组织RNA测序结果表明,ILA可以刺激Th1和Th2和Th17细胞分化通路,可以激活吞噬小体。CCK-8法结果表明,ILA具有抑制人宫颈癌细胞(C33A)的细胞活性作用(P<0.01)。结论 芹糖异甘草苷能够激活免疫系统增加NK细胞的数量,驱动吞噬作用。同时,芹糖异甘草苷还具有抑制肿瘤细胞生长的作用,可用于抗肿瘤药物的开发。
Objective To investigate the effect of isoliquiritin apioside(ILA) on immune function and its anti-tumor effect in mice. Methods C57BL/6 male mice were injected with ILA via tail vein;the cognitive level of mice was measured by water maze;the number of T cells, B cells and NK cells was measured by flow cytometry. The immune function was reconstructed in severely immunodeficient female B-NDG mice by injection of healthy C57BL/6 mouse spleen cells. RNA sequencing of blood and hippocampus of B-NDG mice was performed to analyze the relevant signaling pathways regulated by ILA. The activity of human cervical cancer cells was detected by CCK-8 to explore the relationship between ILA and tumor. Results The water maze test showed that ILA didn’t improve the cognitive ability of mice. Flow cytometry showed that ILA stably increased the number of NK cells in the blood and spleen of normal mice(P<0.01);and also increased the number of NK cells in the spleen of severely immunodeficient mice and promoted NK cell reconstitution(P<0.01). Blood RNA sequencing in B-NDG mice showed that ILA regulated signaling pathways related to platelet activation, focal adhesion, chemokine and FcγR-mediated phagocytosis apoptosis;upregulated Snap23, Rap1b, Fcer1g, Fermt3, p2ry12, Gnai2 gene expression. RNA sequencing of hippocampal tissue in B-NDG mice showed that ILA regulated signal pathways related to Th1, Th2, Th17 cell differentiation, and activating phagocytic vesicles. CCK-8 assay showed that ILA inhibited proliferation of human cervical cancer C33A cells(P<0.01). Conclusion ILA can activate the immune system to increase the number of NK cells and promote phagocytosis in mice, and also inhibit tumor cell proliferation, which is related to regulating various signal pathways.
作者
龚雪
刘海亮
GONG Xue;LIU Hailiang(Ministry of Education Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,College of Life Sciences,Shihezi University,Shihezi 832003,Xinjiang Uygur Autonomous Region,China;Institute for Regenerative Medicine,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200123,China;Translational Medical Center for Stem Cell Therapy,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200123,China)
出处
《同济大学学报（医学版）》
CAS
2023年第1期15-23,共9页
Journal of Tongji University(Medical Science)
基金
科技部重点研发计划(2020YFC2002800)。
关键词
芹糖异甘草苷
免疫系统
抗衰老
抗癌
isoliquiritin apioside
immune system
anti-aging
anti-cancer
