中文摘要：

背景：J2即是以CD4分子与MHCⅡ类分子复合结合物功能域（CD4-D1/MHCⅡβ）为靶点,在数十万种有机化合物化学数据库中进行计算机筛选获得的小分子化合物。在先期的研究中,作者分别采用口服和腹腔注射等全身用药的方式将J2用于小鼠皮肤移植及角膜移植模型,结果证明J2能够延长移植片的生存时间,抑制排斥反应的发生。为了能更好的发挥药物的靶向作用,并减少全身毒副反应,进一步将J2用于局部治疗角膜移植排斥反应。目的：观察新型免疫抑制剂J2对同种异体穿透性角膜移植大鼠模型CD4^＋和CD8^＋T细胞免疫功能的抑制作用。方法：以成年雌性Wistar大鼠作为供体,SD大鼠作为受体,建立同种异体穿透性角膜移植模型。A组为正常SD大鼠结膜下空白溶剂0.05 mL注射组。手术大鼠随机分成3组：B组为SD大鼠自体角膜移植结膜下空白溶剂0.05 mL注射组;C组为同种异体角膜移植结膜下空白溶剂0.05 mL注射组;D组为同种异体角膜移植结膜下1%J2-纳米混悬液（NS）0.05 mL注射组。各组动物分别于移植后3 d、1周、2周、3周,使用流式细胞仪检测外周血中T细胞亚群分布情况并进行比较。结果与结论：B组各时间点外周血中淋巴细胞总CD3^＋、CD4^＋、CD8^＋以及CD4^＋/CD8^＋差异无显著性意义;C组移植后3 d和1周总CD3^＋、CD4^＋、CD8^＋差异无显著性意义,1周和2周总CD3^＋、CD4^＋、CD8^＋数目增多,差异有显著性意义（P〈0.05）;D组中,1周和2周时CD4^＋和CD8^＋无显著增生。同一时间点横向比较：3 d、1周、2周时D组总CD3^＋明显少于C组,差异有显著性意义（P〈0.05）,而在第3周时D组与C组差异无显著性意义;CD4^＋在移植后3 d和1周时D组较C组数目少,但差异无显著性意义。CD4^＋/CD8^＋比值,在3 d、1周、3周时D组与C组比较差异均无显著性意义。提示J2通过抑制T淋巴细胞增生,抑制T细胞介导的角膜移植

英文摘要：

BACKGROUND： J2 takes functional domain（MHC CD4-D1/） of complex conjugate of CD4 molecule and MHC class II molecule as a target, and is a small molecule compound obtained by computer screening from a chemical data containing hundreds of thousands of organic compounds. In the previous study, J2 was used in mouse models of skin transplantation and keratoplasty by oral and intraperitoneal injection. Results verified that J2 could prolong the survival time of grafts, and suppress occurrence of rejection. To better play the role of a drug targeting and to reduce systemic toxicity, J2 will be further utilized in local treatment of keratoplasty rejection. OBJECTIVE： To investigate the inhibitory effect of new immunosuppressive agent J2 on CD4^＋ and CD8^＋ T cell immune functions in rat models receiving allogenic penetrating keratoplasty. METHODS： Allogeneic penetrating keratoplasty model was established using the adult female Wistar rats as donors and Sprague-Dawley rats as recipients. Group A： normal Sprague-Dawley rats were injected with 0.05 mL placebo subconjunctivally. Surgery rats were randomly divided into three groups. Group B： allograft rats were injected with 0.05 mL placebo subconjunctivally after autologous keratoplasty. Group C： allograft rats were injected with 0.05 mL placebo subconjunctivally. Group D： allograft rats were injected with 1% J2-nanosuspension 0.05 mL subconjunctivally. The distribution of T cell subsets in peripheral blood was detected using flow cytometry at 3 days, 1, 2 and 3 weeks after transplantation and compared among groups. RESULTS AND CONCLUSION： There was no significant difference in total CD3^＋ T cells, CD4^＋ T cells, CD8^＋ T cells and CD4^＋/CD8^＋ in peripheral blood lymphocytes in group B at various time points. At 3 days and 1 week after surgery in group C, no significant difference in total CD3^＋ T cells, CD4^＋ T cells and CD8^＋ T cells was detected. At 1 and 2 weeks, the number of total CD3^＋ T cells, CD4^＋ T cells and CD8^＋ T cells