核因子-κB反义核苷酸对大鼠移植角膜存活时间的影响

Influence of neuclear factor-kappa B antisense oligodeoxynucleotides on survival time of rat cornea allografts

目的研究核因子κB(NFκB)反义寡核苷酸对大鼠角膜移植排斥反应的影响。方法使用大鼠穿透角膜移植排斥反应动物模型,观察脂质体包裹的NFκB反义寡核苷酸对排斥反应指数(RI)及植片存活时间的影响,并测定受体鼠脾细胞混合淋巴细胞培养(MLC)和细胞毒T细胞(CTL)活性。结果反义寡核苷酸组角膜植片存活时间较对照组明显延长(P<0.01);MLC显示该组大鼠脾细胞对供体抗原刺激的增殖反应受到抑制(P<0.05),CTL活性明显减弱(P<0.05)。结论脂质体包裹的NFκB反义寡核苷酸能有效抑制受体鼠对移植物的排斥反应,使角膜植片存活时间延长。

ObjectiveTo investigate the effect of antisense phosphorothiate oligodeoxynucleotide of specific for neuclear factor-kappa B in a rat model of penetrating keratoplasty.MethodsCorneal transplantation was performed orthotopically from SD rats to Wistar rats.Various liposomes-mediated antisense oligodeoxynucleotides,blank liposomes and normal solution were subconjunctivally injected respectively in transplanted rats for 5 days.Mean survival time and rejection index of corneas were determined following the injection.Five rats in each group were sacrificed on the 7th day after transplantation,and then mixed lymphocyte culture (MLC) and cytotoxic T lymphocyte(CTL) activity of spleen cells from recipients were detected.ResultsThe survival time of corneal allografts in NF-κB antisense oligodeoxynucleotide group was significantly prolonged than that of control group(P<0.01).MLC showed that proliferative responses of spleen cells to alloantigen stimulation from antisense oligodeoxynucleotide group of recipients were suppressed (P<0.05),and the CTL activity was significantly reduced (P<0.05).ConclusionNF-κB antisense oligodeoxynucleotide mediated by liposomes can effectively inhibit graft rejection and prolong survival time of corneal allografts.