| Part I The set-up of the animal model and efficacy of sirolim-us eye dropsObjectiveTo establish a rat animal model of corneal graft rejection, and toobserve the effects of different dosages of sirolimus eye drops oncorneal allograft rejection, and to explore the optimal therapeuticconcentrations.MethodsSD rats as donors, Wistar rats were used as acceptor to establishcorneal allograft rejection model. These animals were divided into6groups using completely rando-mised design (A～F group). Dropswere administrated four times a day at the second day postoperativ-ely. Group A were matrix drops, sirolimus concentration of grou-p B～E drops were0.25g/L,0.5g/L,1g/L and2g/L respectively, for atotal of14days. According to Larkin, etc. rejection scoring criter-ia, assessment were done to determine the situation after graft reje-ction and compare the average survival time among groups. ResultsThe mean survival time from group A to E were10.50±1.84da-ys,15.30±1.64days,19.80±3.19days,23.10±4.12days and26.10±3.73days respectively.Significant difference was found among groups(F=40.614，P=0.000). The survival time at any group from B to Ewas significantly longer than group A (P value was0.001,0.000,0.000,0.000respectively).Significant difference was found between gr-oup B and any group from C to E (P value was0.002,0.000,0.000respectively). Significant difference was found between group C a-nd group D or group E (P value was0.0021,0.000respectively). S-ignificant difference was found between group D and group E (P=0.035).ConclusionsOrdinary sirolimus eye drops of0.25g/L,0.5g/L,1g/L and2g/L caneffectively prevent cornea immune rejection after low risk corneatransplantation.However2g/L SRL eye drops is more effective thanSRL eye drops of other concentration. Part II The study of the different forms of sirolimus eye dropsand combination therapy for corneal transplant rejectionObjectiveTo investigate the efficacy and mechanisms of2g/L of different f-ormulations of sirolimus eye drops and combination of10g/L aceticacid splashed Nison dragon eye drops,10g/L CsA eye drops treat-ing rat corneal allograft rejection.MethodsSD rats as donors, Wistar rats were used as acceptor to establishcorneal allograft rejection model. These animals were divided into8groups using completely randomised design (A～H group). Drops w-ere administrated four times a day at the second day postoperativel-y. Group A were matrix drops,group B were2g/L SRL ordinary eyedrops, group C were2g/L SRL microemulsion eye drops, group Dwere10g/L acetic acid splashed Nison dragon eye drops, group Ewere10g/L CsA eyedrops, group F were2g/L SRL microemulsioneyedrops with10g/L prednisolone acetate eye drops, group G we-re2g/L SRL microemulsion eyedrops with10g/L CsA eyedrops,and group H were2g/L SRL microemulsion eyedrops with10g/Lprednisolone acetate ophthalmic plus10g/L CsA eye drops for14total days. After2days postoperatively, clinically observed the corn-eal graft under the slit lamp, and determined the condition of the p-ostoperative graft rejection on the basis of Larkin’s assessment crite-rior, and observed when corneal graft rejection, and recorded corne-al survival time. Termination of the experiment when transplant rej- ection medication did not occur after42days application of the dr-ug.ResultsThe mean survival time from group A to H were10.50±1.84da-ys,26.10±3.73days,30.90±6.17days,22.70±5.50days,24.90±5.70da-ys,35.70±5.50days,36.10±5.49days and37.50±5.42days respectivel-y.The survival time at any group from B to H was significantly lo-nger than group A (P value was all0.000respectively).Compare w-ith A,B to H,significant difference was found between group B andgroup from C,F,G,H(P value was0.039,0.000,0.000,0.000respectiv-ely).No significant difference was found between group B and anygroup D,E (P value was0.140,0.600respectively). Significant differ-ence was found between group C and group D to group H (P val-ue was0.001,0.010,0.039,0.026,0.005respectively).Compare with D,E to H,no significant difference was found between group D andgroup E(P value was P=0.338),significant difference was found bet-ween group B and group from F,G,H(P value was all0.000respec-tively).Significant difference was found between group E and anygroup from F to H (P value was all0.000respectively). No signif-icant difference was found between group F and group G,H(P valuewas0.861,0.432respectively).No significant difference was foundbetween group G and group H (P=0.0.541). ConclusionsOrdinary sirolimus eye drops, sirolumus microemulsion eye drops,acetic acid splashed Nison dragon eye drops and CsA eye drops c-an effectively prevent cornea immune rejection after low risk corneatransplantation.However sirolumus microemulsion eyedrops is moreeffective than SRL eye drops of other concentration,combination th-erapy is better than medication alone. |
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