【作者】 辛萌； 史伟云； 吴祥根；

【Author】 XIN Meng,SHI Wei-yun,WU Xiang-gen (State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao,266071, China)

【机构】 山东省眼科研究所； 山东省眼科学重点实验室-省部共建国家重点实验室培育基地；

【摘要】 目的探讨1.0mg霉酚酸酯眼内植入型缓释剂(MMF-DDS)对兔高危角膜移植术后免疫排斥反应的抑制作用,并评价霉酚酸(MPA)房水药物浓度与免疫排斥反应的关系。方法采用角膜基质缝线法诱导兔眼角膜新生血管化建立高危动物模型,对成功诱导角膜新生血管的兔分为空白对照组(A组)、1%霉酚酸酯滴眼液组(B组)、环孢素前房植入组(C组)、MMF-DDS前房植入组(D组)进行同种异体穿透性角膜移植。术后裂隙灯显微镜观察各组角膜植片变化情况,记录各组角膜植片存活时间,并进行眼局部组织学检查,观察组织结构的变化;高效液相检测房水中MPA的药物浓度。结果各组角膜植片存活时间和组织学检查结果表明A、B两组角膜植片发生免疫排斥反应平均时间分别为18.7±3.0天和37.5±6.2天。C组除一只在术后130天发生排斥,其余均未发生免疫排斥反应。D组在观察期内角膜植片透明,均未发生免疫排斥。观察期内,A、B两组免疫排斥反应发生率均为100%,C组和D组免疫排斥反应发生率分别为16.5%和0%。组织学检查表明A、B、C组出现免疫排斥反应的角膜植片厚度增加,基质内大量炎性细胞浸润和新生血管生长。D组角膜植片厚度大致正常,角膜基质中未见明显炎性细胞浸润及新生血管生长。在8周时间内房水中MPA的浓度为0.247μg/ml~4.376μg/ml。结论MMF-DDS能够显著抑制兔高危角膜移植术后免疫排斥反应的发生,大大延长了角膜植片存活时间。MMF-DDS无刺激性,使用安全,具有良好的生物相容性,有望成为一种安全有效的新型眼用免疫排斥抑制药物。更多还原

【Abstract】 OBJECT To investigate the immunosuppressive activity of MMF-DDS in rabbit model of high-risk penetrating keratoplasty. METHOD Corneal vascularization was induced on New Zealand white rabbits by passing 5-0 silk sutures in corneal stroma in each quadrant. The corneal neovascularized rabbits received a unilateral 7-mm diameter central penetrating keratoplasty using ten New Zealand white rabbits as donors,and were divided into four treatment groups: Group A, control group and received no therapy; Group B, 1% MMF eye drop four times daily; Group C, 1.0mg CsA-DDS implanted in the anterior chamber; Group D, 1.0mg MMF-DDS implanted in the anterior chamber. Following up for 150 days, the corneal allografts (opacity, edema and neovascularization) were examined by the slit-lamp biomicroscopy tertian for the first two weeks, twice one week thereafter. Survival time of these animal models was recorded in four groups.Histochemical and ultrastructural studies were carried out on the procured specimens of corneal allografts. Concentrations of MMF and MPA in aqueous humor were detected by HPLC. RESULTS Survival time of corneal allografts and histopathologic examinations: Mean survival time of A and B trial groups were 18.7±2.98, 37.5±6.24 (p=0.005) days respectively. Allografts of group C were transparent except one allograft showed up imunne rejection after130 days. Allografts of group D were transparent in entire period. The incidence of allografts rejection was 100% in group A and B, 16.5% and 0% in group C and D respectively. The rejected allografts were much more edematous and heavier infiltrated with leukocytes than nonrejected allografts. Concentrations of MPA in aqueous humor were 0.247μg/ml~4.376μg/ml in two months. CONCLUSION MMF-DDS could prolong high-risk allograft survival time and significantly inhibited corneal immune rejection in the rabbit model of penetrating keratoplasty.更多还原