角膜移植模型大鼠急性排斥期应用转化生长因子β1对肿瘤坏死因子α的影响  

Effects of transforming growth factor-beta1 on tumor necrosis factor-alpha expression of corneal allografts during acute immunological rejection in rats

作　　者：王恒[1] 陆晓和 左炜[1] 

机构地区：[1]深圳市第四人民医院眼科,广东省深圳市518000

出　　处：《中国组织工程研究》2015年第5期778-782,共5页Chinese Journal of Tissue Engineering Research

摘　　要：背景:同种异体角膜移植是目前治疗角膜盲最有效的方法。然而角膜移植排斥反应的发生率居高不下,研制高效低毒的免疫抑制药物是亟待解决的问题。目的:建立角膜移植大鼠模型,在植片急性排斥期,检测空白对照组和使用转化生长因子β1滴眼液植片组的肿瘤坏死因子α的表达。方法:建立同种异体穿透性角膜移植模型大鼠,随机分为空白对照组;1%环孢素A滴眼组(环孢素A组);转化生长因子β1滴眼组(转化生长因子β1组),从术后第1天开始用药,1滴/次,3次/d;术后所有受大鼠术眼点0.3%氧氟沙星滴眼液、0.5%托品酰胺滴眼液,3次/d,第12天停药。取角膜植片行苏木精-伊红染色以及免疫组织化学染色(SABC法)检测角膜植片中肿瘤坏死因子α在各组角膜组织的表达及分布情况。结果与结论:苏木精-伊红染色显示:空白对照组植片显著增厚,大量单核细胞和淋巴细胞浸润,转化生长因子β1滴眼液组角膜植片厚度正常,无明显炎性细胞浸润。免疫组织化学显性:转化生长因子β1滴眼液组的植片肿瘤坏死因子α阳性细胞数量均较空白对照组减少(P<0.05)。提示转化生长因子β1滴眼液可减少角膜移植模型大鼠急性排斥期植片中肿瘤坏死因子α蛋白的表达,而且可以减少炎症细胞对角膜植片的浸润,这可能就是转化生长因子β1抗排斥的主要机制之一。BACKGROUND：Al ogeneic penetrating keratoplasty is the most effective method for treating corneal blindness. However, the incidence of rejections is high after keratoplasty, so it is urgent to develop an immunosuppressive drug with high efficacy and low toxicity. OBJECTIVE：To establish al ogeneic penetrating keratoplasty models and monitor the expression of tumor necrosis factor-αin blank control group and after transforming growth factor-β1 eyedrop during acute rejection period of corneal grafts. METHODS：Al ogeneic penetrating keratoplasty models were established and were randomly divided into blank control group, ciclosporin A group （1%ciclosporin A）, and transforming growth factor-β1 group （1μg/ml transforming growth factor-β1 eyedrop）. The medications from each group commenced at 1 day after surgery, one eyedrop once, three eyedrops per day. Al the operated eyes were given 0.3%ofloxacin ophthalmic solutions and 0.5%tropicaide ophthalmic solution, three times per day, for 12 days. The corneal grafts were harvested for hematoxylin-eosin staining and immunihistochemical staining （SABC method）, to detect tumor necrosis factor-αexpression in corneal grafts. RESULTS AND CONCLUSION：Hematoxylin-eosin staining showed that, corneal grafts were significantly thickened, a large number of histoleucocytes and lymphocytes infiltrated in the blank control group;corneal grafts showed normal thickness and no inflammatory cel s infiltrated in the transforming growth factor-β1 group.＆amp;nbsp;Immunohistochemical staining showed that, there were less cel s positive for tumor necrosis factor-αin the transforming growth factor-β1 group compared with the blank control group （P〈0.05）. Transforming growth factor-β1 eyedrops can reduce the expression of tumor necrosis factor-αin the corneal grafts during acute rejection period, and reduce the inflammatory cel s infiltration in the corneal grafts, which is probably the mechanism of transforming growth factor-β1 to prevent and treat corneal al ograf

关 键 词：实验动物 移植 角膜移植 排斥反应 转化生长因子Β1 肿瘤坏死因子Α 

分 类 号：R318[医药卫生—生物医学工程]