复方黄黛片对急性早幼粒细胞白血病动物模型坏死性凋亡的影响

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关键词:复方黄黛片;急性早幼粒细胞白血病;坏死性凋亡;MLKL蛋白;裸鼠中图分类号:R285.5 文献标志码:A 文章编号:1007-3213(2025)11-2816-07DOI:10.13359/j.cnki. gzxbtcm.2025.11.027

Abstract:Objective To investigate the therapeutic efectsand mechanism of Compound Huangdai Tablets on nude mice with acute promyelocytic leukemia(APL).Methods An APL xenograft model was established in nude mice using NB4 cells.Succesfully modeled mice were divided into a control group and low-and high-dose Compound Huangdai Tablets groups.The grouping intervention wasas folow:the low-and high-dose Compound Huangdai Tablets groups were administered Compound Huangdai Tablets solution (suspended in 0.5% sodium carboxymethyl cellulose solution) by gavage at doses of 545 and 1090mg⋅kg-1 ,respectively,while the control group received an equal volume of normal saline.The administration was performed twice daily,with each dose being O.2 mL,foratotaldurationof25days.The generalcondition,tumor volume,and tumor weight were observed. Reactive oxygen species (ROS)levels in tumor tissues were measured.Western Blot and immunohistochemistry (IHC)were used to detect the expresion levels of key necroptosis molecules,including mixed lineage kinase domain-like protein(MLKL),receptor-interacting protein kinase 1(RIPK1),and receptor-interacting protein kinase 3(RIPK3).Results Mice in the Compound Huangdai Tablets groups showed no abnormal mental status, suden weight loss,or feeding diffculties.There was no significant difference inbody mass among the groups ( P> 0.05).Compared with the control group,the high-dose Compound Huangdai Tablets group showed significantly reduced tumor volume and mass ( P<0.05 ),along with increased ROS levels in tumor tissues( P<0.05 ). The expression levels of MLKL,RIPK1,and RIPK3 proteins in tumor tisues of the high-dose group were higher than those in the control group ( P<0.05 ).Conclusion Compound Huangdai Tablets promote necroptosis in nude mice with acute promyelocytic leukemia by activating MLKL protein.

KeyWords:Compound Huangdai Tablets;acute promyelocytic leukemia(APL);necroptosis;MLKL;nude mice

急性早幼粒细胞白血病(acutepromyelocyticleukemia,APL)是急性髓细胞白血病(AML)的一个特殊亚型,占AML的 10%~15%[1] ,表现为外周血、骨髓中早幼粒细胞增多, 90% 的APL患者出现t(15;17)( q22 ;q21)、PML-RARα等分子和遗传学特异性改变。(剩余8590字)

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