Effects Of Artemisinin And Its Derivatives On Rat Corneal Transplantation

ObjectiveThe aim is to investigate effects of artemisinin and its derivatives on ratcorneal transplantation, to further explore the possible mechanism.MethodsWith Wistar rats as donor, SD rats as receptor for penetrating keratoplasty.Recipient rats were randomly divided into5groups: Negative control group;Positive control group; Cyclosporine A group; Artemisinin group; Artesunategroup. Among them, the negative control group, without any treatment. Theremaining four groups were received allogeneic corneal transplantationoperation, respectively, administrated by1%CMC-Na solution1.5mL,cyclosporine A10mg/kg, artemisinin600mg/kg and artesunate200mg/kg,since the operation day to the12thday after transplantation.After the operation, we observed the condition of corneal plants, recordingthe survival time. The14th days after operation, checking the corneal tissuepathology. The changing over the mRNA of IL-2、IL-17and CCR1would bemeasured by RT-PCR. ELISA was used to detect the change of IL-4and IL-2inrats aqueous humor.ResultsThe corneal graft median survival time of positive control group, CsA group,Artemisinin and Artesunate group was (11.67±0.67) days,(20.50±0.76) days,(18.67±0.67) days and (16.33±0.49) days. Compared with the positive control group, the other groups is significantly prolonged. And the survival time ofAtemisinin group is longer than the Artesunate, but not as good as theCyclosporine A group. Histopathology shows the plants of the positive controlgroup is thicken great and ande edema seriously, the structure is disordered,and neovascularization and infiltration by a large number of inflammatory cells.Cyclosporin A group graft is almost no edema, and mild inflammatory cellinfiltration. Artemisinin and artesunate group are similar, light edema, a smallamount of inflammatory cell infiltrated, which is superior to the positive controlgroup. RT-PCR reveals: cytokines IL-2, IL-17and CCR1are higer in the positivecontrol group compared with other groups. There is significant differencebetween the expression of IL-17and CCR1, when Artemisinin group andArtesunate group (there is no statistically significant difference between them)are compared with Cyclosporin A group. There was no difference betweenartemisinin group and cyclosporine A group on the expression of IL-2, but betterthan Artesunate group. ELISA discloses IL-2, IL-4are appeared in aqueoushumor of artemisinin, artesunate group, and no statistically significant differencebetween the two groups, and the expression of IL-2is lower than the positivecontrol group, but higher than that cyclosporin A group. While, the expression ofIL-4is higher than positive control group, lower than Cyclosporine A group, thedifference are significant statistically. These cytokines are slight expression innormal cornea and aqueous humor, but compared with the other four groupshave obvious differences.Conclusions1. Administrated with Artemisinin and its derivatives, Artesunate afterpenetrating keratoplasty, can prolong corneal grafts survival time obviously,inhibit transplantation immune rejection. Deducing the Artemisinin drugs playthe role of immunesuppression on corneal graft rejection. 2. The mechanism of Artemisinin drugs inhibiting corneal transplantationimmune rejection, may be related to inhibiting the synthesis and secretion ofcytokines IL-2, IL-17and CCR1, and increasing the expression of IL-4.