摘要
目的探讨雷帕霉素(RAPA)对大鼠角膜移植排斥反应的防治效果。方法以SD大鼠为供体,Wistar大鼠为受体建立角膜移植实验模型。采用完全随机分组设计方案,将68只Wistar鼠(68只眼)随机分为4组,A组为Wistar鼠自体原位角膜移植,B、C、D组为SDWistar鼠之间进行同种异体角膜移植。术后灌胃给药,A组和B组给予空白液,C组和D组分别给予RAPA(3mg·kg-1·d-1)和环孢霉素A(CsA)(10mg·kg-1·d-1),连续用药12d。根据Holland排斥反应评分系统,判断术后植片排斥情况。比较各组角膜植片的平均存活时间和植片存活率。采用广义估计方程对角膜的新生血管评分进行统计学分析。术后14d,对各组角膜进行组织学检查。结果RAPA组发生排斥反应的时间明显延迟,同种异体移植对照组植片平均存活时间(MST)为(11.0±1.5)d,RAPA组MST为(36.1±14.9)d,两组比较差异有统计学意义(P<0.05)。RAPA组角膜植片存活情况较CsA组好,但两组植片存活率比较差异无统计学意义(P>0.05)。RAPA组术后角膜新生血管的生长明显低于异体移植对照组(P<0.05)和CsA组(P<0.05)。组织学检查证实,术后14d,RAPA组角膜植片未见明显淋巴细胞浸润。结论口服RAPA能够延缓大鼠角膜移植排斥反应的发生,并能够抑制术后新生血管的生成。
Objective To investigate the effects of rapamycin on prevention of corneal allograft rejection in murine corneal transplantation. Methods The outbred strain SD and Wistar rats were used as donors and recipients, respectively. Sixty-eight Wistar rats were divided into four groups： Group A, autograft control; Group B, allograft control （the control groups were given placebo only） ; Group C and D, allograft groups, were treated with orally RAPA （3 mg · kg^-1 · d^-1） and CsA （10 mg · kg^-1 · d^-1）, respectively. The drugs were delivered for 12 days beginning at the day of transplantation. Each animal was examined by operating microscopy. The grafts were evaluated clinically by means of Holland＇s scoring system and graft survival was assessed by Kaplan-Meier analysis. The neovascular indexes of rejection were compared among different groups. Histological examination on ocular tissues was performed on day 14 to confirm the clinical diagnosis of rejection. Results The average transplant survival time in the allogenic control （ Group B） was （ 11.0 ± 1.5） d. Treatment with RAPA （Group C） led to a statistically significant prolongation of transplant survival to （36. 1 ± 14. 9） d （P 〈 0. 05）. Treatment with RAPA 3 mg · kg^-1 · d^-1 prolonged transplant survival as compared with treatment with CsA （Group D）, but the difference was not statistically significant （P 〉 0. 05 ） . Corneal neovascularization was induced after the surgery. In RAPA group, corneal neovascularization was markedly reduced as compared with allograft control （ Group B） （ P 〈 0. 05） and CsA group （ Group D） （ P 〈 0. 05 ）. Fewer inflammatory cells were found in the corneal stroma of the RAPA group. Conclusion These results show that oral immunosuppression with RAPA can prevent corneal graft rejection and corneal neovascularization. （Chirr J Ophthalmol, 2005,41：930-935 ）
出处
《中华眼科杂志》
CAS
CSCD
北大核心
2005年第10期930-935,共6页
Chinese Journal of Ophthalmology
关键词
角膜移植
移植物排斥
西罗莫司
Corneal transplantation
Graft rejection
Sirolimus
