摘要/Abstract
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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