上海交通大学学报(医学版) ›› 2019, Vol. 39 ›› Issue (9): 1011-.doi: 10.3969/j.issn.1674-8115.2019.09.012

• 论著·基础研究 • 上一篇    下一篇

顺铂通过杀伤粒样髓系抑制细胞促进膀胱癌小鼠心力衰竭

伍科1*,姚智显 1*,郑重1*,程蕾蕾 2,刘志宏 1   

  1. 1. 上海交通大学附属第一人民医院泌尿外科临床医学中心,上海 200080;2. 复旦大学附属中山医院心脏超声诊断科,上海 200032
  • 出版日期:2019-09-28 发布日期:2019-11-02
  • 通讯作者: 刘志宏,电子信箱:drzhihongliu@sjtu.edu.cn。
  • 作者简介:伍科(1990—),男,博士生;电子信箱: doctorwuke@163.com。姚智显( 1993—),男,硕士生;电子信箱: yao50985098@gmail.com。郑重(1995—),男,硕士生;电子信箱: drzhengzhong@163.com。*为共同第一作者。
  • 基金资助:
    上海市教育委员会高峰高原学科建设计划(20172019)

Cisplatin promotes heart failure in bladder cancer miceimpairing granulocytic myeloid-derived suppressor cells

WU Ke1*, YAO Zhi-xian1*, ZHENG Zhong1*, CHENG Lei-lei2, LIU Zhi-hong1   

  1. 1. Clinical Medicine Center of Urology Department, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; 2. Department of Cardiac Ultrasound Diagnosis, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • Online:2019-09-28 Published:2019-11-02
  • Supported by:
    Shanghai Municipal Education Commission— Gaofeng Clinical Medicine Support, 20172019)。

摘要: 目的 ·探讨顺铂杀伤粒样髓系抑制细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)对膀胱癌小鼠心力衰竭(心衰)的影响。方法 ·选择 8周龄无特定病原体( specific pathogen free,SPF)级的健康 C3H/He雌性小鼠 50只,皮下注射 MBT-2小鼠膀胱癌细胞构建 C3H/He小鼠膀胱癌模型后,将其分为 A~ E组、每组 10只,并设置 A组为空白对照组。向 B~ E组小鼠连续腹腔注射 5 mg/(kg·d)异丙肾上腺素 14 d,成功构建膀胱癌心衰模型。设置 B组为对照组。每 48 h向 C组小鼠腹腔内注射 7.5 mg/ kg顺铂行化学治疗,于 14 d处死小鼠。采用流式细胞术鉴定 G-MDSCs并进行分离、提纯,每 7 d经尾静脉向 D组小鼠输注提纯的 1×107个 G-MDSCs。E组小鼠以 C、D组方法联合处理。采用苏木精 –伊红染色法对小鼠心肌组织进行染色,并通过心脏质量 /体质量比、倒置相差显微镜下观察的心肌细胞形态及心肌细胞区域面积,分析小鼠的心衰程度。结果 ·流式细胞术结果显示,与 B组相比,C组小鼠循环系统中 G-MDSCs水平明显下降( P0.000)。经苏木精 -伊红染色观察及 Image J软件分析显示, C组小鼠较 B组的心脏质量 /体质量比及心肌细胞区域面积均增加( P0.001,P0.002);而经 G-MDSCs输注后, D组小鼠较 B组的上述 2个指标均有所下降( P0.000,P0.011);经顺铂 /G-MDSCs联合处理后, E组小鼠较 C组的上述 2个指标亦均有所下降( P0.000,P0.001)。结论 · G-MDSCs具有一定的心肌保护作用,顺铂能够通过杀伤 G-MDSCs加速心衰的进程。

关键词: 膀胱癌, 顺铂, 粒样髓系抑制细胞, 心力衰竭

Abstract:

Objective · To investigate the effect of cisplatin on heart failure in bladder cancer miceimpairing granulocytic myeloid-derived suppressor cells (G-MDSCs). Methods · Fifty 8-week-old specific pathogen free (SPF) C3H/He healthy female mice were used to establish the bladder cancer model after subcutaneous injection of MBT-2 mice bladder cancer cells. The mice were divided into group A–E, 10 mice in each group, and the group A was set as the blank control group. The group B–E mice were continuously intraperitoneally injected with 5 mg/ (kg.d) isoproterenol for 14 d to successfully establish the heart failure model. The group B was set as the control group. The mice were intraperitoneally injected with 7.5 mg/kg cisplatin every 48 h for chemotherapy, and killed at 14 d in the group C. G-MDSCs were identified, isolated and purifiedflow cytometry. 1×107 purified G-MDSCs were intravenously injected into the group D mice via the tail vein every 7 d. The group E mice was treatedcombining the procedure of the group C and the group D. The myocardial tissue of the mice was stainedhematoxylin-eosin staining. And the heart failure degree of the mice was analyzedthe heart weight/body weight ratio and the observation under the inverted phase contrast microscope. Results · Flow cytometry results showed that compared with the group B, the level of G-MDSCs in the circulation system of the group C mice was significantly decreased (P0.000). Hematoxylin-eosin staining and Image J software analysis showed that compared with the group B, the heart weight/body weight ratio and the area of myocardial cells of the group C mice were significantly increased (P0.001, P0.002). However, after G-MDSCs injection, the above two indexes in the group D mice were decreased compared with those in the group B (P0.000, P0.011). After cisplatin/G-MDSCs combined treatment, the above two indexes in the group E were also decreased compared with those in the group C (P0.000, P0.001). Conclusion · G-MDSCs have cardioprotective effects, while cisplatin can facilitate heart failureimpairing G-MDSCs.

Key words: bladder cancer, cisplatin, granulocytic myeloid-derived suppressor cells (G-MDSCs), heart failure

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