低强度超声对大鼠多烯紫杉醇化疗所致骨髓抑制的影响及其机制

Impact and mechanism of low intensity ultrasound on bone marrow suppression induced by docetaxel in rats

目的分析低强度超声治疗对大鼠多烯紫杉醇化疗所致骨髓抑制的影响及其机制。方法将40只雌性大鼠随机均分为超声组和对照组,每日腹腔注射多烯紫杉醇(25mg/kg体质量),持续4天。对超声组于第1次多烯紫杉醇注射后当天开始每天行低强度超声辐照,持续7天;对照组同期予以假辐照。分别于注射多烯紫杉醇前、超声辐照开始后第4、7及14天行血常规检查及免疫球蛋白检测。超声辐照开始后第4天,于2组中各随机选取4只大鼠处死,检测干细胞因子(SCF)、细胞间黏附分子-1(ICAM-1)及血管细胞黏附分子-1(VCAM-1)。以组织学方法检测多烯紫杉醇注射前、超声辐照开始后第4、7及14天大鼠右侧股骨骨髓组织有核细胞计数,并观察超声辐照第7天大鼠超声辐照处皮肤和肌肉组织HE染色表现。结果与对照组相比,超声组大鼠辐照开始后第4天外周血白细胞、中性粒细胞及淋巴细胞计数,第7、14天免疫球蛋白A(IgA),第4、14天免疫球蛋白G(IgG)及免疫球蛋白M(IgM)均明显升高(P均<0.05)。超声组大鼠骨髓SCF及ICAM-1信使核糖核酸(mRNA)相对表达水平均明显高于对照组,VCAM-1mRNA相对表达水平明显低于对照组,差异均有统计学意义(P均<0.05)。超声辐照开始后第4、7天,超声组骨髓有核细胞均较对照组明显增多(P均<0.05)。2组大鼠辐照处皮肤及肌肉组织均无明显损伤。结论低强度超声可用于治疗大鼠多烯紫杉醇化疗所致骨髓抑制,其机制可能在于改善骨髓造血微环境。

Objective To analyze the effect and mechanism of low intensity ultrasound on bone marrow suppression induced by docetaxel in rat models.Methods Forty female rats were randomly divided into ultrasound group and control group(each n=20).Daily intraperitoneal injection of docetaxel(25 mg/kg)was given all rats for consecutive 4 days.Rats in ultrasound group were daily irradiated with low intensity ultrasound for consecutive 7 days after the first injection of docetaxel,while rats in control group received false irradiation at the same time.Routine blood examination and immunoglobulin tests were performed before docetaxel injection on the 4 th,7 th and 14 th day of irradiation.On the 4 th day of irradiation,4 rats in each group were randomly selected and killed for detection of stem cell factor(SCF),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1).Histological methods were used to detect the number of nucleated cells in the right femoral bone marrow tissue of rats before injection of docetaxel on the 4 th,7 th and 14 th day after the first time of irradiation.HE staining and pathological examinations of skin and muscle tissues of rats were performed on the 7 th day after the first time of irradiation.Results In ultrasound group,leukocyte,neutrophil and lymphocyte counts in peripheral blood on the 4 th day after the first time of irradiatio,titer of immunoglobulin A(IgA)on the 7 th and 14 th day after the first time of irradiation,titers of immunoglobulin G(IgG)and immunoglobulin M(IgM)on the 4 th and 14 th day after the first time of irradiation increased obviously compared with those of control group(all P<0.05).The relative mRNA expression levels of SCF and ICAM-1 in bone marrow of rats in ultrasound group were significantly higher than those in control group,while the relative mRNA expression level of VCAM-1 in bone marrow of rats in ultrasound group was significantly lower than that in control group(all P<0.05).On the 4 th and 7 th day after the first time of irradiation,the numbers of bone marrow nucleated cells in ultrasound group were significantly higher than those in control group(both P<0.05).There was no obvious damage to the skin and muscle of the irradiated rats in both the two groups.Conclusion Low intensity ultrasound is feasible in treatment of bone marrow suppression induced by docetaxel in rats,and its mechanism may be improvement of bone marrow hematopoietic microenvironment.