强骨生血口服液对小鼠化疗后骨髓抑制的保护作用及机制研究

摘要

Objective:To investigate the protective effect of Qianggushengxue oral liquid (QGSX) on chemotherapy-induced bone marrow suppression in mice.Methods:A total of 192 BALB/c mice with body weight of 20 ·25 g were randomly divided into 6 groups:sham,model group,three QGSX-treatment groups of different doses (3.9,7.8,15.6 mL· kg-1) and a positive drug group treated with Dangguibuxue oral liquid (2.6 mL·kg-1).All animals were orally treated with respective drugs or water once each day for 31 d.In the period of the experiments,except the normal group,bone marrow suppression were induced in the animals in the other 5 groups by combined treatment with acetylphenylhydrazinem (APH) and cyclophosphamide (CP).On the 1 lth,18th,25th and 32th days,8 animals in each group were executed respectively to collect blood samples for blood routine examination and to gather femoral bone marrow for nucleated cell count and cell cycle.The contents and protein expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecules (PECAM-1)were examined by ELISA and Western blotting respectively in femoral bone marrow.Results:QGSX could significantly increase the content of HGB in normal mice and inhibit the decrease in the contents of HGB,PLT and RET ratio in APH-CP-treated mice.Also,QGSX could attenuate the decrease in nucleated cell count and promote the transformation of nucleated cells into S and G2/M cycles.Furthermore,QGSX could increase both the contents and the protein expression of VEGF and PECAM-1 in APH-CP-treated mice.Conclusion:QGSX exhibits protective effects on chemotherapy-induced bone marrow suppression in mice,and its actions are related to the increase in the content of cytikines and modulation of bone marrow microenvironment.%目的:研究强骨生血口服液对小鼠化疗后骨髓抑制的保护作用及机制.方法:SPF级BALB/c小鼠192只,雌雄各半,体重20 ～25 g,随机分为正常对照组、模型对照组、当归补血口服液组、强骨生血口服液低、中、高剂量组6组,每组32只.各组小鼠按20 mL·kg-1灌胃(ig)给予相应剂量药液或纯化水,连续31d.给药期间除正常对照组外,其余各组动物采用乙酰苯肼(APH)和环磷酰胺(CP)联用诱导骨髓抑制模型.分别于给药后d11,d18,d 25和d32各组随机取8只动物眼眶采血,进行血常规指标检测;取股骨骨髓进行有核细胞计数,用流式细胞术检测有核细胞的细胞周期;取另一侧股骨骨髓,采用ELISA法检测骨髓组织血管内皮生长因子(VEGF)、血小板内皮细胞黏附分子(PECAM-1)的含量;采用Western Blot检测骨髓中VEGF和PECAM-1的表达.结果:强骨生血口服液能增加正常小鼠外周血中HGB含量,并能显著增加APH-CP诱导的复合型小鼠骨髓抑制模型的HGB、PLT数量、RET比例、骨髓细胞有核细胞数(P＜0.05),能显著改善APH-CP所致的小鼠骨髓中VEGF和PECAM-1含量下降及VEGF和PECAM-1蛋白表达下调情况(P＜0.05),能显著改善APH-CP对小鼠骨髓G0/G1期阻滞,促进有核细胞细胞进入S期及G2/M其,促进细胞分裂,增强造血功能.结论:强骨生血口服液小鼠化疗后骨髓抑制具有明显保护作用,其机制与增加骨髓细胞因子VEGF和PECAM-1表达,调节骨髓微环境有关.