新型免疫抑制剂J2纳米混悬液抑制大鼠角膜移植排斥反应的实验研究  

Study on a novel immunosuppressant of J2 nano-suspension on rat corneal transplantation rejection

作　　者：郭惠玲[1] 杜改萍[2] 王大江[2] 胡莲娜[1] 伍春荣[1] 高付林[1] 闫洪欣[1] 黄一飞[2] 

机构地区：[1]解放军306医院眼科,北京市100101 [2]解放军总医院眼科,北京市100853

出　　处：《眼科新进展》2015年第7期608-611,共4页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:30973245);全国博士后科学基金面上项目(编号:20100481481)~~

摘　　要：目的观察计算机辅助药物设计的新型免疫抑制剂J2纳米混悬液（nano-suspension,NS）结膜下注射对大鼠角膜移植排斥反应的抑制作用。方法成年雌性Wistar大鼠为供体,Sprague-Dawley（SD）大鼠为受体,建立同种异体穿透性角膜移植模型。手术大鼠随机分成3组,每组各16只（32眼氉）,A组：SD大鼠自体角膜移植,结膜下注射空白溶剂0.05 mL;B、C组为同种异体角膜移植组,术后分别给予结膜下注射空白溶剂0.05 mL及10 g·L-1J2 NS。术后记录角膜植片排斥指数（rejection index,RI）,当RI≥6,确定为排斥。各组于角膜移植后7 d、14 d随机选取2只行术眼及同侧颌下淋巴结病理学检查。结果 A组：术后2~3 d角膜植片由透明逐渐变为混浊、水肿,随后保持透明。B组：术后3~5 d角膜植片开始水肿、混浊,7~10 d时水肿、混浊发展迅速。C组：术后1周反应与A组相似,之后出现角膜水肿、混浊,术后9~14 d角膜完全混浊。A、B、C组的角膜植片生存时间分别为（30.00±0.00）d、（10.75±1.60）d、（14.33±2.93）d,三组间差异有统计学意义（均为P〈0.05）。组织学观察发现：A组术后炎症反应轻微,基质厚度基本正常或增厚,内皮层完整。B组术后14 d时可见典型的免疫排斥反应,植片角膜上皮空泡样改变、部分崩解坏死。C组较B组角膜植片中细胞成分和新生血管均少,同侧颌下淋巴结增生明显减弱。结论 J2 NS结膜下注射有抑制大鼠角膜移植排斥的作用,可减轻角膜移植术后角膜植片和同侧颌下淋巴结的细胞增生,抑制免疫应答。Objective T o investigate the inhibition on the rejection of rat corneal transplantation of novel im m unosuppressant of J2 nano-suspension（ J2-N S）. Methods Allogeneic penetrating keratoplasty m odel w as established by using the adult fem ale W istar rats as donors and Sprague-D aw ley（ SD） rats as recipients. Rats w ere divided into 3 groups,16 cases（ 32eyes） in each group. G roup A：SD rats w ere injected 0. 05 m L placebo subconjunctivally after autograft keratoplasty. G roup B：Allograft rats w ere injected 0. 05 m L placebo subconjunctivally after surgery. G roup C ：Allograft rats w ere injected 10 g·L- 1J2-N S 0. 05 m L subconjunctivally after surgery. T he graft rejection index（ RI） and survival tim e of anim als in each group w ere recorded. If the RI w as m ore than 6,the rejected reaction happened. T he cornea and ipsilateral subm andibular lym ph nodes w ere exam ined pathologically at 7 days,14 days.respectively,after surgery. Results G roup A：T he grafts had a little edem a and opaque from2 days to 3 days postoperatively,w hile after the graft rem ained transparency. G roup B：T he grafts becam e edem a and opaque from 3 days to 5 days postoperatively,and the degree of the edem a and opaque becam e speedy from 7 days to 10 days postoperatively. G roup C ：T he reaction w as sim ilar w ith group A at 1 w eek postoperatively,w hile after the graft becam e edem a and opaque. T he graft rejected reaction happened from 9 days to 14 days. T he survival tim e of group A,B,C w ere（30. 00 ± 0. 00） days,（10. 75 ± 1. 60） days and（14. 33 ± 2. 93） days,there w ere significant differences betw een each tw o groups（ all P〈0. 05）. H istologiy show ed that the inflam m ation w as slightly,the strom a w as norm al and the endothelium w as intact in group A;T he appearance of rejection appeared at 14 days,the corneal epithelium appeared vacuole and necrosis partly in group B. T he cellular com ponents and angiogenesis in all layers of cornea of group C w ere less com pare

关 键 词：免疫抑制剂 角膜移植 排斥反应 颌下淋巴结 

分 类 号：R779.65[医药卫生—眼科]