Systemic application of sphingosine 1-phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice

Systemic application of sphingosine 1-phosphate receptor 1 immunomodulator inhibits corneal allograft rejection in mice
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全身应用 1-磷酸鞘氨醇受体 1 免疫调节剂可抑制小鼠角膜同种异体移植排斥反应。

DOI:
10.1111/aos.12237
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发表时间:
2014-02-01
影响因子:
3.4
通讯作者:
Huang, Yifei
Huang, Yifei
中科院分区:
医学3区
文献类型:
--
作者:
Zhu, Jing;Liu, Yong;Huang, Yifei

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目的:本研究旨在探讨鞘氨醇1-磷酸受体1(S1 P1)对小鼠同种异体角膜移植的影响。方法:112只BALB/c小鼠接受C57 BL/6供体角膜移植。受体随机分为7组,分别腹腔注射S1 P1(5 mg/kg/d)、环孢素A(5 mg/kg/d)、地塞米松(1 mg/kg/d)和雷帕霉素(2 mg/kg/d)。S1 P1与雷帕霉素或环孢霉素A联合应用,生理盐水作为阴性对照。ELISA法检测血清IL-2、IL-10、TGF-1和IFN-γ水平。流式细胞仪检测CD 4 + T细胞和调节性T细胞(Treg)表型。通过实时定量PCR分析细胞因子mRNA表达。免疫荧光染色鉴定CD 4 + T细胞和细胞因子。结果如下:与对照组(MST,14.6 ± 0.2天; n=5,p < 0.05)相比,腹腔注射S1 P1单独(平均存活时间MST,35.3 ± 5.6天)、S1 P1联合雷帕霉素(MST,38.7 ± 6.5天)或S1 P1联合环孢素A(MST,32.7 ± 4.8天)可延长角膜移植物存活时间。
Purpose: This study aims to investigate the effects of systemic application of sphingosine 1-phosphate receptor 1(S1P1) on allogeneic corneal transplantation in mice. Methods: A total of 112 BALB/c mice received corneal grafts from C57BL/6 donors. Recipients were randomly divided into seven groups and treated with intraperitoneal injections of S1P1 (5mg/kg/days), cyclosporine A (5mg/kg/days), dexamethasone (1mg/kg/days) and rapamycin (2mg/kg/days). S1P1was combined with rapamycin or cyclosporine A, and saline served as negative control. Serum levels of IL-2, IL-10, TGF-1 and IFN- were measured by Elisa. The numbers of CD4+ T and regulatory (Treg) cell phenotype were measured by flow cytometry. Cytokine mRNA expression was analysed by real-time quantitative PCR. CD4+ T cells and cytokines were histologically identified by immunofluorescence staining. Results: Corneal graft survival was prolonged by intraperitoneal injections in S1P1 alone (mean survival time MST, 35.35.6days), S1P1 combined with rapamycin (MST, 38.7 +/- 6.5days) or S1P1 and cyclosporine A (MST, 32.7 +/- 4.8days) compared with the controls (MST, 14.6 +/- 0.2days; n=5, p