FTY720对大鼠角膜移植排斥反应的抑制作用

Inhibition of FTY720 on rejection of corneal transplantation in rats

目的研究FTY720对大鼠角膜移植免疫排斥反应的抑制作用。方法 建立同种异体大鼠穿透性角膜移植动物模型,以Wistar大鼠为供体,SD大鼠为受体,随机分成4组,对照组每天4mg·kg-1生理盐水灌胃,CsA组为每天10mg·kg-1CsA(5g.L-1)灌胃,FTY720组为每天0.2mg·kg-1FTY720(0.1g.L-1)灌胃,联合用药组为每天5mg·kg-1CsA(5g.L-1)和0.1mg·kg-1FTY720(0.1g.L-1)灌胃,术后第1天开始灌胃给药,连续用药14d后停药。对各组大鼠术眼角膜植片进行临床观察,对植片的临床指数:混浊度、水肿、新生血管及排斥反应指数进行评分,并记录角膜植片的存活时间。结果 对照组、CsA组、FTY720组和联合用药组角膜植片的存活时间分别为(10.38±1.92)d、(20.13±2.17)d、(21.38±2.72)d、(29.88±3.04)d,各用药组角膜植片的存活时间与对照组比较显著延长(均为P=0.000);联合用药组优于单独用药组(均为P=0.000);FTY720组与CsA组比较差异无统计学意义(P>0.05)。术后14d各用药组角膜植片的混浊度、水肿、角膜新生血管、排斥反应指数均低于对照组(均为P<0.01);联合用药组均优于单独用药组;FTY720组与CsA组比较差异无统计学意义(均为P>0.05)。结论 口服FTY720能显著延长大鼠角膜植片的存活时间,抑制角膜移植免疫排斥反应。CsA与FTY720联合用药具有协同作用,优于单独用药组。

Objective To investigate inhibition of FRY720 on immunological rejection of corneal transplantation in rats. Methods Rat models with penetrating corneal transplantation at allograft rats were made. Wistar rats were donors,and SD rats were receptors. All rats were randomly divided into 4 groups. Rats in control group were taken gastric lavage of 4 mg· kg-1 normal saline everyday; Rats in CsA group were taken gastric lavage of 10 mg · kg-1 CsA（5 g · L-1） everyday;Rats in FTY720 group were taken gastric lavage of 0.2 mg · kg-1 FTY720 （0. 1 g · L-1 ） everyday; Rats in combined drug group were taken gastric lavage of 5 mg· kg-1 （ 5 g · L-1 ） CsA and 0. 1 mg · kg-1 FIT720（0. 1 g· L-1 ） everyday. Gastric lavage was taken at the postoperative 1st day,and stopped at 14 days after application of drugs. Clinical observation of corneal transplants of operative eye was taken in each group. Clinical indices of transplants as turbidity, edema, neovascularization and rejection index were scored, and survival time of corneal transplant was recorded. Results Survival times of corneal transplants were （ 10.38 ± 1.92 ） d, （20. 13 ± 2. 17 ） d, （ 21.38± 2. 72 ） d and （ 29. 88 ± 3.04） d in control group, CsA group, FlaY720 group and combined brug group. The survival time of corneal transplant in each drug group was obviously longer than control group （ all P = 0.000）. Combined drug group was better than single drug groups （ both P = 0. 000 ）. No difference was found between FTY720 group and CsA group （P 〉 0.05 ）.At postoperative 14 days,turbidity, edema, corneal neovascularization and rejection index in each drug group were better than those of control group （ all P 〈 0.01 ）. Combined drug group was better than single drug groups. No difference was found between FTY720 group and CsA group （ all P 〉 0.05 ）. Conelusions Oral administration of FTY720 can significantly prolong the survival time of corneal transplant, and inhibit immunological rejection of corneal transplantation in rats. CsA and FRY720 have synergistic effect, which has better effect than single drug.