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低强度脉冲超声对环磷酰胺所致兔白细胞减少症的治疗作用

Treatment effect of low intensity pulsed ultrasound on leukopenia induced by cyclophosphamide in rabbits.

作者信息

Liu Baoru, Luo Yueping, Luo Dong, Zhou Weichen, Zhang Yu, He Ruixin, Li Junshu, Wang Yong, Wang Yan, Chen Wenzhi

机构信息

State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical UniversityChongqing 400016, China.

Chongqing Collaborative Innovation Center for Minimally-Invasive and Noninvasive MedicineChongqing 400016, China.

出版信息

Am J Transl Res. 2017 Jul 15;9(7):3315-3325. eCollection 2017.

Abstract

OBJECTIVE

This study aims to examine the effects of low intensity pulsed ultrasound (LIPUS) on leukopenia induced by cyclophosphamide in a rabbit model.

METHODS

The leukopenia model in New Zealand rabbit was established by injecting cyclophosphamide into the ear vein. Forty leukopenia model rabbits were randomly allocated to control group (n = 20) and LIPUS group (n = 20). LIPUS group underwent 20 minutes of daily ultrasound treatment at femoral metaphysis for 7 days while control group received sham treatment. Diarrhea rate, mortality and blood cell count were calculated. IgA, IgG and IgM levels were measured by ELISA. Flow cytometry was used to detect CD44, CD49d, and PU.1. HE staining was performed to analyze bone marrow hyperplasia and changes of skin and muscle.

RESULTS

LIPUS treatment significantly promoted the proliferation of bone marrow nucleated cells, increased the number of WBC, IgA, IgG and IgM in the peripheral blood, and reduced the diarrhea rate and mortality. The irradiated skin and muscle tissues showed no obvious damages. LIPUS treatment promoted the migration of hematopoietic cells to peripheral blood by decreasing the expression of CD49d and CD44 on the surface of CD34 positive cells. It also promoted the differentiation of hematopoietic stem cells into granulocytes and lymphocytes by decreasing the expression of PU.1.

CONCLUSION

LIPUS can be used as a safe and effective clinical treatment for cyclophosphamide induced leukopenia.

摘要

目的

本研究旨在探讨低强度脉冲超声(LIPUS)对环磷酰胺诱导的兔白细胞减少症的影响。

方法

通过耳静脉注射环磷酰胺建立新西兰兔白细胞减少模型。将40只白细胞减少模型兔随机分为对照组(n = 20)和LIPUS组(n = 20)。LIPUS组在股骨近端干骺端每日接受20分钟超声治疗,共7天,而对照组接受假治疗。计算腹泻率、死亡率和血细胞计数。采用酶联免疫吸附测定法(ELISA)检测IgA、IgG和IgM水平。运用流式细胞术检测CD44、CD49d和PU.1。进行苏木精-伊红(HE)染色以分析骨髓增生及皮肤和肌肉的变化。

结果

LIPUS治疗显著促进骨髓有核细胞增殖,增加外周血白细胞、IgA、IgG和IgM数量,降低腹泻率和死亡率。照射的皮肤和肌肉组织未显示明显损伤。LIPUS治疗通过降低CD34阳性细胞表面CD49d和CD44的表达促进造血细胞向外周血迁移。它还通过降低PU.1的表达促进造血干细胞向粒细胞和淋巴细胞分化。

结论

LIPUS可作为环磷酰胺诱导的白细胞减少症的一种安全有效的临床治疗方法。

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