复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究

薛程元; 崔美晨; 文旭; 廖镜林; 齐宇镈; 司雨平; 杨茜茹; 韩欣璞; 刘可心; 侯丽

doi:10.16025/j.1674-1307.2025.07.002

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复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究

专题——血液病的中医药治疗 | 更新时间：2025-09-11

- 复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究
- Mechanisms of Compound Huangdai Tablet Formulation in reversing arsenic resistance in mice with acute promyelocytic leukemia
- 北京中医药 2025年44卷第7期页码：820-826
- 作者机构：
  
  北京中医药大学东直门医院血液肿瘤科，北京 100700
- 作者简介：
  
  薛程元，男，28岁，博士研究生。研究方向：中西医结合防治恶性血液病。
  侯丽，E-mail：houli1203@126.com
- 基金信息：
  
  国家自然科学基金资助项目(82074240);中央高水平中医医院临床科研业务费资助项目(CZ015);国家中医药管理局高水平中医药重点学科建设项目中医血液病学(zyyzdxk-2023268)
- DOI：10.16025/j.1674-1307.2025.07.002
  中图分类号：
- 收稿日期：2025-04-25，
  
  纸质出版日期：2025-07-25
- 稿件说明：
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薛程元，崔美晨，文旭，等.复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究［J］.北京中医药，2025，44（7）：820-826.

XUE Chengyuan,CUI Meichen,WEN Xu,et al.Mechanisms of Compound Huangdai Tablet Formulation in reversing arsenic resistance in mice with acute promyelocytic leukemia[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(07):820-826.
薛程元，崔美晨，文旭，等.复方黄黛片组方配伍逆转急性早幼粒细胞白血病小鼠砷剂耐药的机制研究［J］.北京中医药，2025，44（7）：820-826. DOI： 10.16025/j.1674-1307.2025.07.002.

XUE Chengyuan,CUI Meichen,WEN Xu,et al.Mechanisms of Compound Huangdai Tablet Formulation in reversing arsenic resistance in mice with acute promyelocytic leukemia[J]. Beijing Journal of Traditional Chinese Medicine,2025,44(07):820-826. DOI： 10.16025/j.1674-1307.2025.07.002.

摘要

目的

明确复方黄黛片组方对HL-60-早幼粒细胞白血病（PML）

A216V

-维甲酸受体α（RARα）荷瘤小鼠的抗肿瘤效应和逆转砷剂耐药作用机制。

方法

用耐砷HL-60-PML

A216V

-RARα细胞，构建裸鼠移植瘤模型，成模后随机分为模型组、雄黄组、三药（青黛、太子参、丹参）联合组、四药（雄黄、青黛、太子参、丹参）联合组，各5只，分别予生理盐水及各药物饮片水煎剂灌胃，期间记录大鼠体质量变化，测量瘤体体积，2周后取材肿瘤组织。HE染色观察病理形态，TUNEL染色检测细胞凋亡情况，免疫组化检测Ki67表达情况，流式细胞术检测CD33及CD11b表达情况。

结果

三药联合组、四药联合组瘤体体积均小于模型组、雄黄组（

0.01）；雄黄组瘤体体积小于模型组，差异无统计学意义（

0.05）。三药联合组、四药联合组与雄黄组瘤体质量比较，差异无统计学意义（

0.05）。抑瘤率：雄黄组21.93%，三药联合组37.77%，四药联合组43.60%。雄黄组肿瘤细胞排列相对松散，细胞周边呈圆环状空隙；三药联合组肿瘤组织结构明显松散，伴有大量脂肪空泡；四药联合组肿瘤组织结构较杂乱，伴有大量脂肪空泡。与雄黄组比较，三药联合组肿瘤细胞凋亡率低（

0.01），四药联合组肿瘤细胞凋亡率高（

0.01）；与三药联合组比较，四药联合组肿瘤细胞凋亡率高（

0.01）。与雄黄组比较，三药联合组肿瘤组织中Ki-67阳性细胞比例高（

0.01）；与三药联合组比较，四药联合组肿瘤组织中Ki-67阳性细胞比例低（

0.01）。与雄黄组比较，三药联合组CD33表达低（

0.01）；与三药联合组比较，四药联合组CD33表达高（

0.01）。与雄黄组比较，三药联合组CD11b表达呈下降趋势，但差异无统计学意义（

0.05）；四药联合组CD11b表达高（

0.01）；三药联合组与四药联合组间差异亦有统计学意义（

0.01）。

结论

复方黄黛片组方配伍对耐砷急性早幼粒细胞白血病（APL）细胞具有促凋亡、诱导分化，抑制细胞增殖的作用，可逆转砷剂耐药。

Abstract

Objective

To clarify the antitumor effects and mechanisms of Compound Huangdai Tablet formulation in reversing arsenic resistance in HL-60-promyelocytic leukemia （PML）

A216V

-retinoic acid receptor α （RARα） tumor-bearing mice.

Methods

A xenograft model was established in nude mice using arsenic-resistant HL-60-PML

A216V

-RARα cells. After model establishment， the mice were rand

omly divided into model group， realgar group， three-drug combination group， and four-drug combination group， with five mice in each group. Mice were gavaged with normal saline or water decoctions of the corresponding drugs. Body weight and tumor volume were recorded during the experiment， and tumor tissues were collected after 2 weeks. Pathological morphology was observed by HE staining， apoptosis was detected by TUNEL assay， Ki-67 expression was assessed by immunohistochemistry， and CD33 and CD11b expression levels were measured by flow cytometry.

Results

Tumor volumes in the three-drug and four-drug combination groups were significantly smaller than those in the model and realgar groups （

0.01）. Tumor volume in the realgar group was lower than that in the model group， but the difference was not statistically significant （

0.05）. Tumor weights in the three-drug and four-drug groups did not differ significantly from that in the realgar group （

0.05）. Tumor inhibition rates were 21.93% in the realgar group， 37.77% in the three-drug group， and 43.60% in the four-drug group. Histologically， tumors in the realgar group showed relatively loose cell arrangement with pericellular vacuoles； the three-drug group exhibited markedly loose structures with abundant fat vacuoles； the four-drug group displayed more disorganized structures with abundant fat vacuoles. Compared with the realgar group， the apoptosis rate was lower in the three-drug group （

0.01） and higher in the four-drug group （

0.01）. Compared with the three-drug group， the apoptosis rate in the four-drug group was also higher （

0.01）. The proportion of Ki-67 positive cells was higher in the three-drug group than in the realgar group （

0.01）， and lower in the four-drug group than in the three-drug group （

0.01）. Compared with the realgar group， CD33 expression was re

duced in the three-drug group （

0.01） but elevated in the four-drug group relative to the three-drug group （

0.01）. CD11b expression showed a downward trend in the three-drug group compared with the realgar group， though not statistically significant （

0.05）， while it was significantly increased in the four-drug group （

0.01）， with a significant difference also observed between the three- and four-drug groups （

0.01）.

Conclusion

The

Compound Huangdai Tablet

formulation exerts pro-apoptotic and differentiation-inducing effects， and inhibits proliferation in arsenic-resistant acute promyelocytic leukemia （APL） cells， thereby contributing to the reversal of arsenic resistance.

关键词

Keywords

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