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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 prevention and treatment of rapamycin (RAPA) on the rejection of rat corneal allograft. Methods The corneal transplantation model was established by using SD rats as donors and Wistar rats as recipients. A total of 68 Wistar rats (68 eyes) were randomly divided into 4 groups according to a completely randomized design. Group A was Wistar autologous corneal transplantation. Groups B, C and D were allografts of SDWistar transplant. The rats in group A and group B were given blank solution after operation. Groups C and D were given RAPA (3 mg · kg-1 · d-1) and cyclosporin A (CsA) (10 mg · kg-1 · D-1), continuous medication 12d. Holland exclusion reaction scoring system to determine postoperative graft rejection. The mean survival time and the survival rate of the grafts in each group were compared. The corneal neovascularization score was statistically analyzed using the generalized estimation equation. On the 14th postoperative day, the corneas of each group were histologically examined. Results The time to rejection in RAPA group was significantly delayed. The mean survival time (MST) in allograft control group was (11.0 ± 1.5) d and that in RAPA group was (36.1 ± 14.9) d, with statistical difference Significance (P <0.05). The survival of corneal graft in RAPA group was better than that in CsA group, but there was no significant difference between the two groups (P> 0.05). Corneal neovascularization in RAPA group was significantly lower than that in allograft control group (P <0.05) and CsA group (P <0.05). Histological examination confirmed that, after 14 days, RAPA group corneal graft no significant lymphocytic infiltration. Conclusion Oral RAPA can delay the occurrence of corneal graft rejection in rats and can inhibit the angiogenesis after operation.