中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (32): 6042-6046.doi: 10.3969/j.issn.2095-4344.2012.32.029

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

CD28-B7共刺激通路对外周血单个核细胞移植治疗重症肌无力的作用

刘红艳，郭静明，王海燕，叶 松，冉昌丽   

  1. 三峡大学第一临床医学院，宜昌市中心人民医院血液科，三峡大学肿瘤研究所，湖北省宜昌市 443003
  • 收稿日期:2012-02-03 修回日期:2012-07-08 出版日期:2012-08-05 发布日期:2012-08-05
  • 作者简介:刘红艳★，1969年生，硕士，副主任医师，主要从事血液病的基础与临床方面的研究。 liuhy518@163.com

Mechanism of CD28-B7 co-stimulatory pathway to myasthenia gravis treated by peripheral blood mononuclear cells

Liu Hong-yan, Guo Jing-ming, Wang Hai-yan, Ye Song, Ran Chang-li   

  1. Department of Hematology, Yichang Central People's Hospital, the First College of Clinical Medical Science, China Three Gorges University, Three Gorges University Oncology Institute, Yichang 443003, Hubei Province, China
  • Received:2012-02-03 Revised:2012-07-08 Online:2012-08-05 Published:2012-08-05
  • About author:Liu Hong-yan★, Master, Associate chief physician, Department of Hematology, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Three Gorges University Oncology Institute, Yichang 443003, Hubei Province, China liuhy518@163.com

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332

被引次数

1

摘要：

背景：有研究表明，CD28-B7共刺激通路与重症肌无力的发生密切相关，但在干细胞移植治疗重症肌无力过程中的作用机制至今少有报道。
目的：观察CD28-B7共刺激通路在重症肌无力大鼠模型中的表达情况。
方法：40只雌性Lewis大鼠等分为正常组、模型组、佐剂组和移植组。后3组大鼠腹腔注射重症肌无力患者血清制备重症肌无力模型。移植组大鼠连续5 d皮下注射粒细胞集落刺激因子10 μg/(kg•d)动员骨髓中造血干细胞进入外周血，颈动脉采血10 mL，分离获得单个核细胞，加入适量生理盐水调节核细胞浓度至2×109 L-1；环磷酰胺50 mg/kg于移植前第4，3，2天从尾静脉注入，1次/d，移植当天用胰岛素注射针吸取单个核细胞自尾静脉注入，移植成功。佐剂组给予等量生理盐水和环磷酰胺。
结果与结论：移植组大鼠血清抗乙酰胆碱受体滴度、CD28、细胞毒性T淋巴细胞相关抗原4、B7.1及B7.2的表达均显著低于模型组(P < 0.01)；模型组和移植组大鼠血清抗乙酰胆碱受体滴度滴度与细胞毒性T淋巴细胞相关抗原4呈正相关(r=0.236，P=0.001和r=0.215，P=0.013)；移植组大鼠Lennon评分显著低于模型组(P < 0.01)。提示干细胞移植可以通过抑制CD28-B7共刺激信号通路以调节机体的免疫系统。

关键词: 重症肌无力, CD28-B7共刺激通路, 血清乙酰胆碱受体, 细胞毒T淋巴细胞相关抗原4, 外周血单个核细胞移植, 干细胞, 干细胞移植, 组织工程, 再生医学

Abstract:

BACKGROUND: There is evidence that CD28-B7 co-stimulatory pathway is closely related to myasthenia gravis. It remains unclear regarding the mechanism of CD28-B7 co-stimulatory pathway to myasthenia gravis treated by peripheral blood mononuclear cells.
OBJECTIVE: To investigate the expression of CD28-B7 co-stimulatory pathway in a rat model of myasthenia gravis.
METHODS: Forty female Lewis rats were divided into control group, model group, adjuvant group and stem cell transplantation group. Rats in the latter three groups were intraperitoneally administered serum from patients with myasthenia gravis to prepare myasthenia gravis models. Rats in the stem cell transplantation group were subcutaneously administered granulocyte colony stimulating factor 10 μg/kg daily for 5 successive days to mobilize bone marrow hematopoietic stem cells into the peripheral blood. Mononuclear cells were harvested from 10 mL carotid artery blood and then subjected to concentration adjustment to 2×109/L with enough amount of physiological saline. At 4, 3, 2 days before transplantation, 50 mg/kg cyclophosphamide was injected from the tail vein, once a day. On the day of transplantation, mononuclear cells were injected via the tail vein through the use of insulin injection needle. Rats in the model group were given no interventions. Rats in the adjuvant group received equal amounts of physiological and cyclophosphamide.
RESULTS AND CONCLUSION: Titer of serum acetylcholine receptor Ab (AChR Ab titer), CD28, cytotoxic T cell antigen-4, B7.1 and B7.2 expression were significantly greater in the stem cell transplantation group than those in the model group (P < 0.01). AChR Ab titer was positively correlated with cytotoxic T cell antigen-4 in the model and stem cell transplantation groups (r = 0.236, P = 0.001 and r = 0.215, P =0.013). The Lennon scores were significantly lower in the stem cell transplantation group than in the model group (P < 0.01). These findings suggest that stem cell transplantation can regulate organism’s immune system by inhibiting CD28-B7 co-stimulatory pathway.

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