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熊果酸抑制大鼠原位同种异体移植术后角膜移植排斥反应

[Ursolic acid inhibits corneal graft rejection following orthotopic allograft transplantation in rats].

作者信息

Wang Bo, Wu Jing, Ma Ming, Li Ping-Ping, Yu Jian

机构信息

Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2015 Apr;35(4):530-5.

Abstract

OBJECTIVE

To investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation.

METHODS

Forty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1).

RESULTS

The allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found.

CONCLUSION

As a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

摘要

目的

研究熊果酸对大鼠原位角膜移植模型中角膜移植排斥反应的影响。

方法

将48只受体Wistar大鼠分为生理盐水处理的正常对照组(A组)、生理盐水处理的自体移植组(B组)、生理盐水处理的SD大鼠同种异体移植组(C组)和腹腔注射熊果酸(UA)处理的SD大鼠同种异体移植组(D组)。原位移植后,大鼠接受生理盐水或熊果酸(20mg·kg⁻¹·d⁻¹)处理12天。采用Larkin角膜排斥反应评分系统评估移植物,并通过Kaplan-Meier分析评估移植物存活情况。在第14天,采集移植物进行组织学检查、蛋白质印迹分析,并评估白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、核转录因子-κB(NF-κB)p65、血管内皮生长因子(VEGF)和细胞间黏附分子-1(ICAM-1)的表达。

结果

D组同种异体移植物存活时间明显长于C组(29.12±9.58天对9.67±2.16天,P<0.05)。熊果酸处理明显降低了移植物中IL-2、IFN-γ、NF-κBp65、ICAM-1和VEGF的表达水平,并增加了抑制性κBα(IκB-α)的表达,且未发现明显的炎性细胞浸润或角膜新生血管形成。

结论

作为一种NF-κB抑制剂,熊果酸可预防角膜新生血管形成和角膜移植排斥反应,从而促进大鼠原位角膜移植术后移植物的存活。

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