间充质干细胞对VX2肺癌模型化学治疗所致骨髓抑制的干预研究

卢兆桐史岩耿明赵修义代尊强

【摘要】目的观察间充质干细胞(MSC)对兔间变表皮鳞癌瘤株(VX2)肺癌模型化学治疗所致骨髓抑制的治疗作用。方法选用2.5～3.5 kg的新西兰大白兔52只，分为对照组(10只)、化学治疗组(21只)、MSC干预组(21只)。在CT引导下建立VX2肺癌模型，建模成功后开始给予化学治疗组吉西他滨176.5 mg/kg，MSC干预组吉西他滨176.5 mg/kg和MSC (1×106/只)，对照组注射等量的生理盐水，1次/周，3组均治疗3个周期，比较不同时段3组VX2肺癌兔模型的白细胞、红细胞、血红蛋白及血小板水平。结果3组实验兔接种VX2组织块后的胸部CT均可见直径2.5～4.5 cm的高密度影。治疗前，3组VX2肺癌兔模型的白细胞、红细胞、血红蛋白及血小板水平比较差异均无统计学意义(P均>0.05)。治疗3个周期后，3组间白细胞、红细胞、血红蛋白和血小板水平比较差异均有统计学意义(P均<0.01)。其中化学治疗组白细胞、红细胞、血红蛋白、血小板水平均比对照组明显下降(P均<0.05)，MSC干预组白细胞、红细胞、血红蛋白水平低于对照组(P均<0.01)，但血小板水平与对照组比较差异无统计学意义(P>0.05)。MSC干预组白细胞及血小板水平均高于化学治疗组(P均<0.05)。结论MSC可减轻VX2肺癌模型化学治疗所致的骨髓抑制。

【关键词】间充质干细胞；化学治疗；骨髓抑制；兔间变表皮鳞癌瘤株；肺癌

收稿日期：(2015-04-30)

DOI:10.3969/g.issn.0253-9802.2015.10.005

基金项目：国家自然科学青年

通讯作者，郑可国，E-mail：zheng-keguo@163.com

Intervention effect of mesenchymal stem cells on bone marrow suppression induced by chemotherapy in VX2lung cancer modelsLuZhaotong,ShiYan,GengMing,ZhaoXiuyi,DaiZunqiang.Ji’nanMilitaryGeneralHospital，Ji’nan250000,China

Abstract【】ObjectiveTo observe the therapeutic effect of mesenchymal stem cells (MSCs) on bone marrow suppression induced by chemotherapy in the VX2 lung cancer rabbit models. MethodsFifty two New Zealand white rabbits, weighing 2.5～3.5 kg, were randomly divided into the control (n=10), chemotherapy (n=21) and intervention groups (n=21). The VX2 lung cancer models were established under CT guidance. After model establishment, the chemotherapy was performed using gemcitabine 176.5mg/kg in the chemotherapy group, gemcitabine 176.5 mg/kg and MSCs (1×106/ rabbit) were administered in the intervention group and equivalent amount of normal saline was injected in the control group, once weekly for three cycles of treatment. The levels of leukocyte, red blood cell, hemoglobin and platelet count among three groups were statistically compared at different time points. ResultsChest CT revealed the signs of high-intensity shadow with a diameter of 2.5～4.5 cm after injecting VX2 tumor cells. Prior to treatment, the leukocyte, red blood cell, hemoglobin and platelet count did not significantly differ among three groups (all P>0.05). After three cycles of therapy, statistical significance was observed among three groups regarding these indexes (all P<0.01). The mean values of four indexes in the chemotherapy were considerably lower compared with those in the control group (all P<0.05). In the MSCs intervention group, leukocyte, red blood cell, hemoglobin levels were significantly decreased compared with those in the control group (P<0.01), whereas the platelet count did not significantly differ between two groups (P>0.05). The leukocyte and platelet count in the MSC intervention group were significantly higher compared with those in the chemotherapy group (both P<0.05). Conclusion MSC could alleviate the bone marrow suppression induced by chemotherapy in VX2 lung cancer models.

【Key words】Mesenchymal stem cell; Chemotherapy; Bone marrow suppression;

VX2tumor lineage; Lung cancer

在恶性肿瘤的治疗中，化学治疗是最常用的治疗方法，随着新辅助化学治疗广泛应用于临床，化学治疗药物的毒副反应也随之增加[1]。研究表明，化学治疗所致骨髓抑制的发生率可达60%以上，临床上减轻骨髓抑制的药物主要为升白细胞类药物，其价格昂贵且不良反应较多，因而在控制骨髓抑制方面仍需要寻找更为有效的方法[2]。间充质干细胞(MSC)，是一种具有自我复制能力和多向分化潜能的成体干细胞，对骨髓中的造血干细胞不仅有机械支持作用，还能分泌多种生长因子支持造血功能。为此……