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不同剂量 FTY720 对大鼠心脏移植模型淋巴细胞细胞周期阻滞的影响。

Effects of different dose of FTY720 on lymphocyte cell cycle arrest in cardiac transplantation model of rats.

机构信息

Department of Urology and Transplantation, First Affiliated Hospital, Binzhou Medical University, Binzhou City, Shandong Province, China.

出版信息

Immunopharmacol Immunotoxicol. 2010 Dec;32(4):680-7. doi: 10.3109/08923971003674433. Epub 2010 Mar 5.

DOI:10.3109/08923971003674433
PMID:20201753
Abstract

PURPOSES

To probe into immunosuppressive effect and cell cycle arrest effect of different dose of FTY720.

METHOD

we study immunosuppressive effect and cell cycle arrest effect of different dose of FTY720 and time and dose dependence of FTY720 with control and random method in vivo, respectively.

RESULTS

(i) survival time of graft in rat cardiac transplantation model is prolonged in group treated with FTY720. It is longer in group treated with FTY720 10 mg/kg than that in group treated with FTY720 2 mg/kg. (ii) The mean sum of lymphocyte in periphery blood decrease obviously 2 h after administration, reaches its peak 4 h after administration, and then maintain at low level stably. The mean sum of lymphocyte shows a linear relationship with dose of FTY720 and decrease with increasing of dose of FTY720. (iii) The percent of cell in G1-G0 increased in group treated with FTY720, not only in thymus but also in lymph node; this is more prevalent in the group treated with FTY720 10 mg/kg than that in group treated with FTY720 2 mg/kg. Similarly, the percent of cell in S and G2-M decreased in group treated with FTY720, not only in thymus but also in lymph node, and this decrease is more associated with group treated with FTY720 10 mg/kg than the one treated with FTY720 2 mg/kg.

CONCLUSION

FTY720 is an effective immunosuppressant and immunosuppressive effect of FTY720 show a tendency of time and dose dependent. Effect of cell cycle arrest of FTY720 is related to dose of this new immunosuppressant.

摘要

目的

探讨不同剂量 FTY720 的免疫抑制作用和细胞周期阻滞作用。

方法

采用体内对照和随机分组的方法,分别研究不同剂量 FTY720 的免疫抑制作用和细胞周期阻滞作用以及 FTY720 的时间和剂量依赖性。

结果

(i)FTY720 治疗组大鼠心脏移植模型移植物存活时间延长,FTY720 10mg/kg 治疗组存活时间长于 FTY720 2mg/kg 治疗组。(ii)给药后 2 小时外周血淋巴细胞总数明显下降,4 小时达到高峰,然后稳定在低水平。外周血淋巴细胞总数与 FTY720 剂量呈线性关系,随 FTY720 剂量的增加而减少。(iii)FTY720 治疗组 G1-G0 期细胞比例升高,不仅在胸腺,而且在淋巴结;FTY720 10mg/kg 治疗组比 FTY720 2mg/kg 治疗组更为明显。同样,FTY720 治疗组 S 和 G2-M 期细胞比例下降,不仅在胸腺,而且在淋巴结,这种下降与 FTY720 10mg/kg 治疗组更为相关,而与 FTY720 2mg/kg 治疗组关系不大。

结论

FTY720 是一种有效的免疫抑制剂,其免疫抑制作用呈时间和剂量依赖性。FTY720 的细胞周期阻滞作用与这种新型免疫抑制剂的剂量有关。

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Effects of different dose of FTY720 on lymphocyte cell cycle arrest in cardiac transplantation model of rats.不同剂量 FTY720 对大鼠心脏移植模型淋巴细胞细胞周期阻滞的影响。
Immunopharmacol Immunotoxicol. 2010 Dec;32(4):680-7. doi: 10.3109/08923971003674433. Epub 2010 Mar 5.
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FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate receptors.新型免疫调节剂FTY720通过对1-磷酸鞘氨醇受体的激动活性,抑制淋巴细胞从次级淋巴组织和胸腺中逸出。
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