Effects of Topical Sphingosine-1-Phosphate 1 Receptor Agonist on Corneal Allograft in Mice
Effects of Topical Sphingosine-1-Phosphate 1 Receptor Agonist on Corneal Allograft in Mice
复制标题
局部鞘氨醇-1-磷酸1受体激动剂对小鼠同种异体角膜移植物的影响。
DOI：
10.1097/ico.0000000000000077
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发表时间：
2014-04-01
期刊：
影响因子：
2.8
通讯作者：
Huang, Yifei
中科院分区：
文献类型：
--
作者：
Jia, Liang;Liu, Yong;Huang, Yifei
目得：本研究的目的是比较局部选择性鞘氨醇-1-磷酸1受体（S1 P1）激动剂和环孢素A（CsA）对小鼠同种异体角膜移植物的抗排斥作用。所有小鼠接受来自28个C57 BL/6供体的角膜移植物。角膜移植术后分别用0.25%、0.5%S1P1激动剂混悬液滴眼或1%CsA滴眼，4次/d。对照组未接受治疗。对角膜移植片进行成像并进行临床评分。移植后14天的切除角膜切片使用苏木精-伊红染色用于组织病理学评价。免疫组织化学染色鉴定角膜标本中CD 86+和MHC-II+树突状细胞。实时定量PCR检测白细胞介素2（IL-2）、干扰素γ（IFN-γ）和细胞毒性T淋巴细胞抗原4（CTLA-4）mRNA的表达。结果：与对照组相比，0.5%S1P1激动剂和1%CsA治疗组角膜移植片存活时间明显延长（P < 0.01）。此外，局部应用0.5%S1P1增加角膜移植物的细胞毒性T淋巴细胞抗原4 mRNA表达。结论：局部应用0.5%S1P1激动剂和1%CsA均能有效延长小鼠角膜移植物的存活时间
PURPOSE: The aim of this study was to compare the antirejection effects of topical selective sphingosine-1-phosphate 1 receptor (S1P1) agonist and cyclosporine A (CsA) on the acceptance of a transplanted, allogeneic cornea graft in a murine animal model.METHODS: Fifty-six BALB/c mice were randomly divided into 4 groups. All the mice received corneal grafts from 28 C57BL/6 donors. Experimental recipients were treated with 0.25%, 0.5% S1P1 agonist suspension eye drops or 1% CsA eye drops 4 times a day after the corneal graft was performed. Controls received no treatment. The corneal grafts were imaged and evaluated with clinical scoring. The excised corneal sections 14 days after transplantation were stained using hematoxylin-eosin for histopathological evaluation. CD86+ and MHC-II+ dendritic cells in corneal samples were identified by immunohistochemical staining. The expression of mRNA in the cornea was evaluated using real-time quantitative PCR for interleukin-2, interferon-gamma, and cytotoxic T-lymphocyte antigen 4.RESULTS: Corneal graft survival was prolonged by treatment with 0.5% S1P1 agonist and 1% CsA (P < 0.01, respectively) when compared with that in the control in clinical scoring. In addition, topical application of 0.5% S1P1 increased the cytotoxic T-lymphocyte antigen 4 mRNA expression of the corneal grafts. There were significant differences observed with 0.5% S1P1 and agonist 1% CsA (P < 0.01, respectively) when compared with the values of the control group in histology scoring.CONCLUSIONS: Topical 0.5% S1P1 agonist is as effective as 1% CsA, and both can effectively prolong the survival of corneal allografts in mice