[关键词]
[摘要]
目的 通过荷瘤动物实验,从外周血血细胞比例、免疫细胞亚型及细胞因子相关指标等方面研究消岩汤对骨髓抑制的影响。方法 Lewis肺癌细胞接种小鼠,荷瘤小鼠ip环磷酰胺(CTX)100 mg/(kg·d),连续3 d,制备荷瘤小鼠化疗后骨髓抑制模型。成模小鼠随机分为模型组、消岩汤组、吉粒芬组、消岩汤与吉粒芬联用组(联用组),每组10只,另取正常小鼠10只为对照组,消岩汤组ig消岩汤水煎液18.2 g/(kg·d),分2次给药,连用7 d,吉粒芬组sc吉粒芬12μg/kg,连用7 d,联用组为两药合用。观察各组小鼠一般血常规、外周血免疫细胞亚群、血清中白细胞介素-3(IL-3)、白细胞介素-6(IL-6)、促红细胞生成素(EPO)、粒细胞巨噬细胞刺激因子(GM-CSF)的变化。结果 与对照组比较,模型组小鼠外周血白细胞(WBC)、红细胞(RBC)、血红蛋白(Hb)、血小板数量(PLT)降低(P<0.05),尤以WBC减少为主(P<0.05);模型组CD3+CD8+T、CD4+CD8+T、CD4/CD8明显降低(P<0.05);模型组小鼠血清中IL-3、IL-6水平明显降低(P<0.05)。与模型组比较,消岩汤组和吉粒芬组WBC数值均增加(P<0.05),消岩汤组、联用组CD3+CD8+T、CD4+CD8+T明显提高(P<0.05),各组NK细胞比较无显著差异(P>0.05),消岩汤组和联用组显著升高小鼠血清中IL-3、IL-6、EPO、GM-CSF水平,吉粒芬组显著升高IL-3、IL-6水平(P<0.05)。与吉粒芬组比较,联用组小鼠外周血WBC增加更明显(P<0.05),且RBC、PLT增加更显著(P<0.05),Treg细胞明显减少(P<0.05)。结论 消岩汤能改善化疗后骨髓抑制小鼠的外周血象,以及T细胞亚群的免疫功能,改善化疗后骨髓抑制程度,且消岩汤与吉粒芬联用效果更佳,其机制可能与促进小鼠血清造血因子IL-3、IL-6、EPO、GM-CSF的生成,从而缓解化疗导致的骨髓抑制程度有关。
[Key word]
[Abstract]
Objective To study the effects and mechanism of Xiaoyan Decoction on bone marrow suppression in mice from aspects of peripheral blood cell ratio, immune function, and cytokines. Methods A mouse model of bone marrow suppression was established. Fifty mice were randomly divided into five groups (n=10):control group, model group, Xiaoyan Decoction group, rhG-CSF group, and Xiaoyan Decoction combined with rhG-CS group. Lewis-tumor mice in Xiaoyan Decoction group were ig given Xiaoyan Decoction 18.2 g/(kg·d) twice daily, for 7 d. Lewis-tumor mice in rhG-CS group were treated by sc injection of rhG-CSF. The routine blood test, immunological functions of peripheral blood and cytokines (IL-3, IL-6, EPO, and GM-CSF) in serum were detected. Results The bone marrow suppression model was successfully established. Compared with control group, the levels of WBC, RBC, Hb, and PLT in peripheral blood of model group were decreased, especially in WBC (P<0.05). There is a remarkable increase in the level of WBC in Xiaoyan Decoction group and rhG-CS group as compared with model group (P<0.05). Contrasted with model group, a significant increasing of CD3+CD8+T cells and CD3+CD8+cells on peripheral blood lymphocytes was observed in Xiaoyan Decoction group and combined group. The level of Treg cell in combined group was significantly less than that of Treg cell in rhG-CS group (P<0.05). And there was no difference in NK cell level among all these groups (P>0.05). The concentration of IL-3 and IL-6 was dramatically reduced in model group compared with control group (P<0.05). And it showed an obviously increasing trend in IL-3, IL-6, EPO, and GM-CSF levels in Xiaoyan Decoction group and combined group, as well as an increase in IL-3, IL-6 levels in rhG-CS group (P<0.05). Conclusion It shows that Xiaoyan Decoction combined with rhG-CS can improve the level of WBC and immunological functions of peripheral blood in bone marrow suppression model mice. And the effect of combination of both drugs is more significant. This might be related to the effect of promoting the production of serum hematopoietic regulator such as IL-3, IL-6, EPO, and GM-CSF, and relieving chemotherapy-induced bone marrow suppression.
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[基金项目]
国家自然科学基金资助项目(81273937);天津市科委自然科学基金青年项目(13JCQNJC10900);天津市抗癌重大专项攻关计划(12ZCDZSY15800)