Wu Xiao-Song, Wu Jing, Ma Ming, Lu Xiao-Li, Yu Jian, Zhang Zhen-Yu
Department of Ophthalmology, 2Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2016 Dec 20;36(12):1677-1683.
To examine expression of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in rat cornea tissue and their role in corneal allograft rejection.
With 15 Wistar rats as the normal control group, 22 Wistar rats received autologous corneal graft transplantation, and 44 Wistar rats received transplantation of corneal graft from SD rats with penetrating keratoplasty. From the rats with allograft transplantation, 22 were selected randomly for treatment with TobraDex eye drops for 30 days after the operation (twice a day), and the remaining 22 rats were treated with normal saline only. Clinical assessment of the corneal grafts was carried out using Larkin's method; histopathological observation, immunohistochemistry, and real-time quantitative PCR of the corneal grafts were performed on days 5 and 9 after the transplantation.
Graft rejection occurred in none of the rats in autograft group. In rats treated with TobraDex, the graft survival time was significantly longer than that in rats with saline treatment (24∓0.32 vs 10∓0.36 days, P<0.001), and histopathological examination revealed numerous inflammatory cells and neovascularization in the allografts in the latter group. SDF-1 and CXCR4 mRNA expression in the corneal tissue increased significantly in rats receiving allograft transplantation and saline treatment (P<0.001 on day 5 and P<0.01 on day 5), and their expression was obviously lowered in rats with TobraDex treatment. Immunohistochemical examination revealed that the expression of SDF-1 and CXCR4, found mainly in the corneal epithelium and stroma, was significantly increased in the allografts in rats with saline treatment.
SDF-1/CXCR4 may participate in corneal graft rejection in rats early after transplantation possibly through the mechanism that SDF-1 specifically induces CXCR4 cell maturation and chemotaxis toward the allograft to promote corneal neovascularization.
检测基质细胞衍生因子-1(SDF-1)和CXC趋化因子受体4(CXCR4)在大鼠角膜组织中的表达及其在角膜移植排斥反应中的作用。
15只Wistar大鼠作为正常对照组,22只Wistar大鼠接受自体角膜移植,44只Wistar大鼠接受SD大鼠穿透性角膜移植。在接受同种异体移植的大鼠中,随机选取22只在术后用妥布霉素地塞米松滴眼液治疗30天(每日2次),其余22只大鼠仅用生理盐水治疗。采用Larkin法对角膜移植片进行临床评估;在移植后第5天和第9天对角膜移植片进行组织病理学观察、免疫组织化学和实时定量PCR检测。
自体移植组大鼠均未发生移植排斥反应。用妥布霉素地塞米松治疗的大鼠,其移植片存活时间明显长于用生理盐水治疗的大鼠(24±0.32天对10±0.36天,P<0.001),组织病理学检查显示后一组同种异体移植片中存在大量炎性细胞和新生血管。接受同种异体移植并经生理盐水治疗的大鼠角膜组织中SDF-1和CXCR4 mRNA表达显著增加(第5天P<0.001,第9天P<0.01),而在妥布霉素地塞米松治疗的大鼠中其表达明显降低。免疫组织化学检查显示,主要在角膜上皮和基质中发现的SDF-1和CXCR4表达在生理盐水治疗的大鼠同种异体移植片中显著增加。
SDF-1/CXCR4可能在移植后早期参与大鼠角膜移植排斥反应,其机制可能是SDF-1特异性诱导CXCR4细胞成熟并向同种异体移植物趋化,从而促进角膜新生血管形成。